1168 lines
92 KiB
HTML
1168 lines
92 KiB
HTML
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<head><title></title></head>
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<body>
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<h1></h1>
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<p></p>
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<blockquote>
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<h2>
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<span style="color: #222222"><span style="font-family: Helvetica"><span><strong>Fats, functions &
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malfunctions</strong></span></span></span>
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</h2>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span><strong>Saturated fatty acids
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terminate the stress reactions, polyunsaturated fatty acids amplify them.</strong></span
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></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span><strong>The most highly unsaturated
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fats, including DHA, accumulate with aging, and their toxic fragments are increased in
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Alzheimer's disease. </strong></span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span><strong>The most highly unsaturated
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fats found in fish oil break down into chemicals that block the use of glucose and
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oxygen.</strong></span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span><strong>The ratio of saturated fatty
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acids to polyunsaturated fatty acids is decreased in cancer. Omega-3 fats promote
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metastasis.</strong></span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Around the beginning of the 20th
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century, it was commonly believed that aging resulted from the accumulation of insoluble
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metabolic by-products, sort of like the clinker ash in a coal furnace. Later, age pigment or
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lipofuscin, was proposed to be such a material. It is a brown pigment that generally increases
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with age, and its formation is increased by consumption of unsaturated fats, by vitamin E
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deficiency, by stress, and by exposure to excess estrogen. Although the pigment can contribute
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to the degenerative processes, aging involves much more than the accumulation of insoluble
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debris; aging increases the tendency to form the debris, as well as vice versa.</span></span
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></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>There is a growing recognition that
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a persistent increase of free fatty acids in the serum, which is seen in shock, heart failure,
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and aging, indicates a bad prognosis, but there is no generally recognized explanation for the
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fact that free fatty acids are harmful. I want to mention some evidence showing that it is the
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accumulation of polyunsaturated fats in the body that makes them harmful.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The physical and functional
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properties of saturated fatty acids and polyunsaturated fatty acids (PUFA) are as different from
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each other as day is from night. The different fatty acids are directly involved, very often
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with opposite effects, in cell division and growth, cell stability and dissolution, the
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organization of cells, tissues, and organs, the regulation of pituitary hormones, adrenalin and
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sympathetic nervous activation, histamine and serotonin synthesis, adrenal cortex hormones,
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thyroid hormones, testosterone, estrogen, activators of the immune system and inflammation
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(cytokines), autoimmune diseases, detoxification, obesity, diabetes, puberty,
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epilepsy, </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Parkinson's disease, other
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degenerative nerve diseases and Alzheimer's disease, cancer, heart failure, atherosclerosis, and
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strokes. In each of these situations, the PUFA have harmful effects.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Most people are surprised to hear
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about the systematically harmful effects of the common dietary polyunsaturated fats and the
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protective effects of saturated fats. That's because there is a pervasive mythology of fats in
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our culture. Officials are proposing to tax saturated fats. Laws are being passed prescribing
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the fats that can be served in restaurants, and people write letters to editors about them, and
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great amounts of money are spent publicizing the importance of eating the right fats. Their
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focus is on obesity, atherosclerosis, and heart disease. The details of the myth change a
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little, as new fat products and industries appear. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>As I understand the basic myth, the
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difference between the "essential" polyunsaturated fats and the saturated fats has to do with
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their shape---the unsaturated fatty acids bend or fold in a way that makes them more mobile than
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saturated fats of the same length, and this causes the all-important "membranes" of cells to be
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more fluid, and thus to have "better functions," though the myth isn't very clear on the issue
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of fluidity and functionality. At that point, it passes responsibility to the more fundamental
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biological myth, of the metabolically active cell membrane. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Practically everyone learns, in
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grade school and from television, about the good and the bad oils, and cell membranes, but it
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might seem likely that people who spend their lives investigating the role of fats in organisms
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would have acquired a different, more complicated, view. But one of the most famous food fat
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researchers, J.M. Bourre, has succinctly (and thoughtlessly) expressed his understanding of the
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function of fatty substances in the body: "In fact the brain, after adipose tissue, is the organ
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richest in lipids, whose only role is to participate in membrane structure." (J.M. Bourre,
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2004.) The fact that his editor let him publish the statement shows how the myth functions,
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causing people to accept things because they are "common knowledge." The influence of the
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medical and pharmaceutical industries is so pervasive that it becomes the context for most
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biological research.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Luckily, many people are working
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outside the myth, in specialized problems of physiology and cell biology, and their observations
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are showing a reality much more complex and interesting than the mythology. </span></span
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></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>When we eat more protein or
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carbohydrate than we need, the excess can be converted to fats, to be stored (as triglycerides),
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but even on a maintenance diet we synthesize some fats that are essential parts of all of our
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cells, including a great variety of phospholipids. People seldom talk about the importance of
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fats in the nucleus of the cell, but every nucleus contains a variety of lipids--phospholipids,
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sphingolipids, cholesterol, even triglycerides--similar to those that are found elsewhere in the
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cell and in every part of the body, including the brain (Balint and Holczinger, 1978; Irvine,
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2002). Phospholipids are often considered to be "membrane lipids," but they have been
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demonstrated in association with elements of the cell's skeleton, involved in cell division,
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rather than in membranes (Shogomori, et al., 1993).</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The cytoskeleton, a fibrous
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framework of the cell that's responsible for maintaining the organized structure of the cell,
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internal movement of organelles, coordination, locomotion, and cell division, is made up of
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three main kinds of protein, and all of these are affected differently by different kinds of
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fat. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Actions of lipids on the cell
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skeleton can change cells' movements, migrations, and invasiveness. Unsaturated fats cause
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clumping of some types of cell filament, condensation and polymerization of other types, in ways
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that are associated with brain degenerative diseases and cancer. For example, DHA alters the
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structure of the protein alpha-synuclein, causing it to take the form seen in Parkinson's
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disease and other brain conditions. The synucleins regulate various structural proteins, and are
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affected by stress, aging, and estrogen exposure, as well as by the polyunsaturated fats. One
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type of synuclein is involved in the promotion of breast cancer. Saturated fatty acids have
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exactly the opposite effects of PUFA on the synucleins, reversing the polymerization caused by
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the PUFA (Sharon, et al., 2003). </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>When cancers are metastasizing,
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their phospholipids contain less stearic acid than the less malignant tumors (Bougnoux, et al.,
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1992), patients with advanced cancer had less stearic acid in their red blood cells (Persad, et
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al., 1990), and adding stearic acid to their food delayed the development of cancer in mice
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(Bennett, 1984). The degree of saturation of the body's fatty acids corresponds to resistance to
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several types of cancer that have been studied (Hawley and Gordon, 1976; Singh, et al.,
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1995).</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The phospholipids are being
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discussed in relation to drugs that can modify "signaling" by acting on phospholipid receptors,
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using language that was developed in relation to hormones. A surface barrier membrane, with
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receptors that send signals to the nucleus, is invoked by many of the recent discussions of
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phospholipids. There's no question that the fats do affect regulatory processes, but the theory
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and the language should correspond to the physiological and ecological realities. Vernadski's
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metaphor, that an organism is a "whirlwind of atoms," is probably more appropriate than
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"targeted signals and receptors" for understanding the physiology of fatty acids and
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phospholipids. The rate of change and renewal of these structural fats is very high. In rats,
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one study found a 30% decrease in the total phospholipid pool in the brain in the first 30
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minutes after death (Adineh, et al., 2004). Another study in the brains of living rats
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found that a particular class of brain lipids, ethanolamine plasmalogens, had a turnover time of
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about 5 hours (Masuzawa, et al., 1984). (This type of lipid is an important component of the
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lipoproteins secreted by the liver into the serum [Vance, 1990], and is also a major lipid in
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the heart and brain.) Stresses such as the loss of sleep cause great distortions in
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phospholipid metabolism throughout the body, especially in the brain and liver.</span></span
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></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Actions of lipids on the cell
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skeleton can change cells' movements, migrations, and invasiveness, even in short term
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experiments. The effects of the "essential fatty acid" linoleic acid have been compared to the
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drug colchicine, which is known to interfere with the cell skeleton and cell division. According
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to Hoover, et al., (1981), it disturbed the structure of the cytoskeleton more than colchicine
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does; it caused the cell filaments to clump together, while saturated fatty acids didn't have
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such an effect.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The fatty molecules that participate
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in the normal cell functions are made by cells even when they are grown in a fat-free solution
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in a culture dish. They include saturated fatty acids such as palmitate and stearate, and
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omega-9 unsaturated fats, such as oleic acid and omega-9 polyunsaturated fatty acids. The
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saturated fatty acids found in the nucleus associated with the chromosomes are resistant to
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change when the composition of the animal's diet changes (Awad and Spector, 1976), while the
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unsaturated fats change according to the diet. These intracellular fats are essential for cell
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division and the regulation of the genes, and for cell survival (Irvine, 2002). Although cells
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make the saturated fats that participate in those basic functions, the high rate of metabolism
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means that some of the lipids will quickly reflect in their structure the free fatty acids that
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circulate in the blood. The fats in the blood reflect the individual's diet history, but
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recently eaten fats can appear in the serum as free fatty acids, if the liver isn't able to
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convert them into triglycerides.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The polyunsaturated fatty acids
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differ from the saturated fats in many ways, besides their shape and their melting temperature,
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and each type of fatty acid is unique in its combination of properties. The polyunsaturated
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fatty acids, made by plants (in the case of fish oils, they are made by algae), are less stable
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than the saturated fats, and the omega-3 and omega-6 fats derived from them, are very
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susceptible to breaking down into toxins, especially in warm-blooded animals. Other differences
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between saturated and polyunsaturated fats are in their effects on surfaces (as surfactant),
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charges (dielectric effects), acidity, and their solubility in water relative to their
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solubility in oil. The polyunsaturated fatty acids are many times more water soluble than
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saturated fatty acids of the same length. This property probably explains why only palmitic acid
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functions as a surfactant in the lungs, allowing the air sacs to stay open, while unsaturated
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fats cause lung edema and respiratory failure.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The great difference in water/oil
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solubility affects the strength of binding between a fatty acid and the lipophilic, oil-like,
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parts of proteins. When a protein has a region with a high affinity for lipids that contain
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double bonds, polyunsaturated fatty acids will displace saturated fats, and they can sometimes
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displace hormones containing multiple double bonds, such as thyroxine and estrogen, from the
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proteins that have a high specificity for those hormones. Transthyretin (also called prealbumin)
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is important as a carrier of the thyroid hormone and vitamin A. The unsaturation of vitamin A
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and of thyroxin allow them to bind firmly with transthyretin and certain other proteins, but the
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unsaturated fatty acids are able to displace them, with an efficiency that increases with the
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number of double bonds, from linoleic (with two double bonds) through DHA (with six double
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bonds). </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The large amount of albumin in the
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blood is important in normal fatty acid binding and transport, but it is also an important part
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of our detoxifying system, since it can carry absorbed toxins from the intestine, lungs, or skin
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to the liver, for detoxification. Albumin facilitates the uptake of saturated fatty acids by
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cells of various types (Paris, et al., 1978), and its ability to bind fatty acids can protect
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cells to some extent from the unsaturated fatty acids (e.g., Rhoads, et al., 1983). The liver's
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detoxification system processes some polyunsaturated fats for excretion, along with hormones and
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environmental toxins.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The movement of proteins from the
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plasma into cells has often been denied, but there is clear evidence that a variety of proteins,
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including IgG, transferrin haptoglobin, and albumin can be found in a variety of cells, even in
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the brain (Liu, et al., 1989). Cells are lipophilic, and absorb molecules in proportion to their
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fattiness; this long ago led people to theorize that cells are coated with a fat
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membrane. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The idea of a semipermeable
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membrane, similar in function to the membrane inside an egg shell, was proposed about 150 years
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ago, to explain the ability of living cells to concentrate certain chemicals, such as potassium
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ions, while excluding others, such as sodium ions. This idea of a molecular sieve was shown to
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be invalid when radioactive isotopes made it possible to observe that sodium ions diffuse freely
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into cells, and it was replaced by the idea of a metabolically active membrane, containing
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"pumps" that made up for the inability to exclude various things, and that allowed cells to
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retain high concentrations of some dissolved substances that are free to diffuse out of the
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cell. The general idea of the membrane as a barrier persisted as a sort of "common sense" idea,
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that has made people ignore experiments that show that some large molecules, including some
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proteins, can quickly and massively enter cells. Albumin and transthyretin are two proteins that
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are sometimes found in large quantities inside cells, and their primary importance is that they
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bind and transport biologically active oily molecules. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>While the competition by PUFA for
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protein binding sites blocks the effects of thyroid hormone and vitamin A, the action of PUFA on
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the sex steroid binding protein (SBP, or SSBG, for sex steroid binding globulin) increases the
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activity of estrogen. That's because the SSBG neutralizes estrogen by binding it, keeping it out
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of cells; free PUFA keep it from binding estrogen (Reed, et al., 1986). People with low
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SSBG/estrogen ratio have an increased risk of cancer. When the SSBG protein is free of estrogen,
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it is able to enter cells, and in that estrogen-free state it probably serves a similar
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protective function, capturing estrogen molecules that enter cells before they can act on other
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proteins or chromosomes. Transthyretin, the main transporter of thyroid and vitamin A, and
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albumin (which can also transport thyroid hormone) are both able to enter cells, while loaded
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with thyroid hormone and vitamin A. Albumin becomes more lipophilic as it binds more lipid
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molecules, so its tendency to enter cells increases in proportion to its fat burden. Albumin in
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the urine is a problem associated with diabetes and kidney disease; albumin loaded with fatty
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acids passes from the blood into the urine more easily than unloaded albumin, and it is the
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fatty acids, not the albumin, which causes the kidney damage (Kamijo, et al., 2002). It's
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possible that SSBG's opposite behavior, entering cells only when it carries no hormones, is the
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result of becoming less lipophilic when it's loaded with estrogen.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Since most people believe that cells
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are enclosed within a barrier membrane, a new industry has appeared to sell special products to
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"target" or "deliver" proteins into cells across the barrier. Combining anything with fat makes
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it more likely to enter cells. Stress (which increases free fatty acids and lowers cell energy)
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makes cells more permeable, admitting a broader range of substances, including those that are
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less lipophilic. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>Linoleic acid and arachidonic acid,
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which are said to "make the lipid membrane more permeable," in fact make the whole cell more
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permeable, by binding to the structural proteins throughout the cell, increasing their affinity
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for water, causing generalized swelling, as well as mitochondrial swelling (leading to reduced
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oxidative function or disintegration), allowing more calcium to enter the cell, activating
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excitatory processes, stimulating a redox shift away from oxidation and toward inflammation,
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leading to either (inappropriate) growth or death of the cell. </span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>When we don't eat for many hours,
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our glycogen stores decrease, and adrenaline secretion is increased, liberating more glucose as
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long as glycogen is available, but also liberating fatty acids from the fatty tissues. When the
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diet has chronically contained more polyunsaturated fats than can be oxidized immediately or
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detoxified by the liver, the fat stores will contain a disproportionate amount of them, since
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fat cells preferentially oxidize saturated fats for their own energy, and the greater water
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solubility of the PUFA causes them to be preferentially released into the bloodstream during
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stress.</span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>In good health, especially in
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children, the stress hormones are produced only in the amount needed, because of negative
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feedback from the free saturated fatty acids, which inhibit the production of adrenalin and
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adrenal steroids, and eating protein and carbohydrate will quickly end the stress. But when the
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fat stores contain mainly PUFA, the free fatty acids in the serum will be mostly linoleic acid
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and arachidonic acid, and smaller amounts of other unsaturated fatty acids. These PUFA stimulate
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the stress hormones, ACTH, cortisol, adrenaline, glucagon, and prolactin, which increase
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lipolysis, producing more fatty acids in a vicious circle. In the relative absence of PUFA, the
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stress reaction is self limiting, but under the influence of PUFA, the stress response becomes
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self-amplifying. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>When stress is very intense, as in
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trauma or sepsis, the reaction of liberating fatty acids can become dangerously
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counter-productive, producing the state of shock. In shock, the liberation of free fatty acids
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interferes with the use of glucose for energy and causes cells to take up water and calcium
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(depleting blood volume and reducing circulation) and to leak ATP, enzymes, and other cell
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contents (Boudreault and Grygorczyk, 2008; Wolfe, et al., 1983; Selzner, et al, 2004; van der
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Wijk, 2003), in something like a systemic inflammatory state (Fabiano, et al., 2008) often
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leading to death. </span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: Helvetica"><span>The remarkable resistance of
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"essential fatty acid deficient" animals to shock (Cook, et al., 1981; Li et al., 1990; Autore,
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et al., 1994) shows that the polyunsaturated fats are centrally involved in the maladaptive
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reactions of shock. The cellular changes that occur in shock--calcium retention, leakiness,
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reduced energy production--are seen in aging and the degenerative diseases; the stress hormones
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and free fatty acids tend to be chronically higher in old age, and an outstanding feature of old
|
|
age is the reduced ability to tolerate stress and to recover from injuries.</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Despite the instability of
|
|
polyunsaturated fatty acids, which tend to break down into toxic fragments, and despite their
|
|
tendency to be preferentially liberated from fat cells during stress, the proportion of them in
|
|
many tissues increases with age (Laganiere and Yu, 1993, 1987; Lee, et al., 1999; Smidova, et
|
|
al., 1990;Tamburini, et al., 2004; Nourooz-Zadeh J and Pereira, 1999 ). This progressive
|
|
increase with age can be seen already in early childhood (Guerra, et al., 2007). The reason for
|
|
this increase seems to be that the saturated fatty acids are preferentially oxidized by many
|
|
types of cell, (fat cells can slowly oxidize fat for their own energy maintenance). Albumin
|
|
preferentially delivers saturated fatty acids into actively metabolizing cells such at the heart
|
|
(Paris, 1978) for use as fuel. This preferential oxidation would explain Hans Selye's results,
|
|
in which canola oil in the diet caused the death of heart cells, but when the animals received
|
|
stearic acid in addition to the canola oil, their hearts showed no sign of damage.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Since healthy cells are very
|
|
lipophilic, saturated fatty acids would have a greater tendency to enter them than the more
|
|
water soluble polyunsaturated fats, especially those with 4, 5, or 6 double bonds, but as cells
|
|
become chronically stressed they more easily admit the unsaturated fats, which slow oxidative
|
|
metabolism and create free radical damage. The free radicals are an effect of stress and aging,
|
|
as well as a factor in its progression.</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>When stress signals activate enzymes
|
|
in fat cells to release free fatty acids from the stored triglycerides, the enzymes in the
|
|
cytoplasm act on the surface of the droplet of fat. This means that the fatty acids with the
|
|
greatest water solubility will be liberated from the fat to move into the blood stream, while
|
|
the more oil soluble fatty acids will remain in the droplet. The long chain of saturated carbon
|
|
atoms (8 in the case of oleic acid, 15 in palmitic acid, and 17 in stearic acid) in the "tail"
|
|
of oleic, palmitic, and stearic acid will be buried in the fat droplet, while the tail of the
|
|
n-3 fatty acids, with only 2 saturated carbons, will be the most exposed to the lipolytic
|
|
enzymes. This means that the n-3 fatty acids are the first to be liberated during stress, the
|
|
n-6 fatty acids next. Saturated and monounsaturated fatty acids are selectively retained by fat
|
|
cells (Speake, et al., 1997).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Women are known to have a greater
|
|
susceptibility than men to lipolysis, with higher levels of free fatty acids in the serum and
|
|
liver, because of the effects of estrogen and related hormones. </span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Women on average have more DHA
|
|
circulating in the serum than men (Giltay, et al., 2004; McNamara, et al., 2008; Childs, et al.,
|
|
2008). This highly unsaturated fatty acid is the first to be liberated from the fat stores under
|
|
stress, and, biologically, the meaning of estrogen is to mimic stress. Estrogen and
|
|
polyunsaturated fatty acids have similar actions on cells, increasing their water content and
|
|
calcium uptake. Long before the Women's Health Initiative reported in 2002 that the use of
|
|
estrogen increased the risk of dementia, it was known that the incidence of Alzhemer's disease
|
|
was 2 or 3 times higher in women than in men. Men with Alzheimer's disease have higher levels of
|
|
estrogen than normal men (Geerlings, et al., 2006). The amount of DHA in the brain (and other
|
|
tissues) increases with aging, and its breakdown products, including neuroprostanes, are
|
|
associated with dementia. Higher levels of DHA and total PUFA are found in the plasma of
|
|
demented patients (Laurin, et al., 2003).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Another interesting association of
|
|
the highly unsaturated fats and estrogen in relation to brain function is that DHA increases the
|
|
entry of estrogen into the pregnant uterus, but inhibits the entry of progesterone (Benassayag,
|
|
et al., 1999), which is crucial for brain cell growth. When Dirix, et al., (2009) supplemented
|
|
pregnant women with PUFA, they found that fetal memory was impaired. </span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>The crucial mitochondrial
|
|
respiratory enzyme, cytochrome c oxidase, declines with aging (Paradies, et al., 1997), as the
|
|
lipid cardiolipin declines, and the enzyme's activity can be restored to the level of young
|
|
animals by adding cardiolipin. The composition of cardiolipin changes with aging, "specifically
|
|
an increase in highly unsaturated fatty acids" (Lee, et al., 2006). Other lipids, such as a
|
|
phosphatidylcholine containing two myristic acid groups, can support the enzyme's activity
|
|
(Hoch, 1992). Even supplementing old animals with hydrogenated peanut oil restores mitochondrial
|
|
respiration to about 80% of normal (Bronnikov, et al., 2010). </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Supplementing thyroid hormone
|
|
increases mitochondrial cardiolipin (Paradies and Ruggiero, 1988). Eliminating the
|
|
polyunsaturated fats from the diet increases mitochondrial respiration (Rafael, et al.,
|
|
1984).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Excitotoxicity is the process in
|
|
which activation of a nerve cell beyond its capacity to produce energy injures or kills the
|
|
cell, by increasing intracellular calcium. Glutamic acid and aspartic acid are the normal
|
|
neurotransmitter excitatory amino acids. Estrogen increases the activity of the excitatory
|
|
transmitter glutamate (Weiland, 1992), and glutamate increases the release of free fatty acids
|
|
(Kolko, et al., 1996). DHA (more strongly even than arachidonic acid) inhibits the uptake of the
|
|
excitotoxic amino acid aspartate, and in some situations glutamate, prolonging their actions.
|
|
Thymocytes are much more easily killed by stress than nerve cells, and they are easy to study.
|
|
The PUFA kill them by increasing their intracellular calcium. The toxicity of DHA is greater
|
|
than that of EPA, whose toxicity is greater than alpha-linolenic acid, and linoleic acid was the
|
|
most potent (Prasad, et al., 2010). Excitotoxicity is probably an important factor in
|
|
Alzheimer's disease (Danysz and Parsons, 2003).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>When the brain is injured, DHA and
|
|
arachidonic acid contribute to brain edema, weakening the blood-brain-barrier, increasing
|
|
protein breakdown, inflammation, and peroxidation, while a similar amount of stearic acid in the
|
|
same situation caused no harm (Yang, et al., 2007). In other situations, such as the important
|
|
intestinal barrier, EPA and DHA also greatly increased the permeability (Dombrowsky, et al.,
|
|
2011).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>The process by which excitotoxicity
|
|
kills a cell is probably a foreshortened version of the aging process. </span></span></span
|
|
>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Excitotoxins (including endotoxin)
|
|
increase the formation of neuroprostanes and isoprostanes (from n-3 and n-6 PUFA) (Milatovic, et
|
|
al., 2005), and acrolein and other fragments, which inhibit the use of glucose and oxygen.
|
|
DHA and EPA produce acrolein and HHE, which react with lysine groups in proteins, and modify
|
|
nucleic acids, changing the bases in DNA. </span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Increased intracellular calcium
|
|
activates lipolysis (by phospholipases), producing more free fatty acids, as well as excitation
|
|
and protein breakdown, and in the brain neurodegenerative diseases, calcium excess contributes
|
|
to the clumping of synuclein (Wojda, et al., 2008), an important regulator of the cytoskeletal
|
|
proteins. The reduced function of normal synuclein makes cells more susceptible to
|
|
excitotoxicity (Leng and Chuang, 2006).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>If the cells adapt to the increased
|
|
calcium, rather than dying, their sensitivity is reduced. This is probably involved in the
|
|
"defensive inhibition" seen in many types of cell. In the brain, DHA and arachidonic acid
|
|
"brought the cells to a new steady state of a moderately elevated [intracellular calcium] level,
|
|
where the cells became virtually insensitive to external stimuli. This new steady state can be
|
|
considered as a mechanism of self-protection" (Sergeeva, et al., 2005). In the heart, the PUFAs
|
|
decreased the sensitivity to stimulation (Coronel et al., 2007) and conduction velocity
|
|
(Tselentakis, et al., 2006; Dhein, et al., 2005). Both DHA and EPA inhibit calcium-ATPase (which
|
|
keeps intracellular calcium low to allow normal neurotransmission) in the cerebral cortex; this
|
|
suggests "a mechanism that explains the dampening effect of omega-3 fatty acids on neuronal
|
|
activity" (Kearns and Haag, 2002).</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>In normal aging, most processes are
|
|
slowed, including nerve conduction velocity, and conduction velocity in the heart (Dhein and
|
|
Hammerath, 2001). A similar "dampening" or desensitization is seen in sensory, endocrine, and
|
|
immune systems, as well as in energy metabolism. Calorie restriction, by decreasing the
|
|
age-related accumulation of PUFA (20:4, 22:4, and 22:5), can prevent the decrease of
|
|
sensitivity, for example in lymphoid cells (Laganier and Fernandes, 1991). The known effects of
|
|
the unsaturated fats on the organizational framework of the cell are consistent with the changes
|
|
that occur in aging.</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>One of the essential protective
|
|
functions that decline with aging is the liver's ability to detoxify chemicals, by combining
|
|
them with glucuronic acid, making them water soluble so that they can be excreted in the urine.
|
|
The liver (and also the intestine and stomach) efficiently process DHA by glucuronidation
|
|
(Little, et al., 2002). Oleic acid, one of the fats that we synthesize ourselves, increases
|
|
(about 8-fold) the activity of the glucuronidation process (Krcmery and Zakim, 1993; Okamura, et
|
|
al., 2006). However, this system is inhibited by the PUFA, arachidonic acid (Yamashita, et al.,
|
|
1997), and also by linoleic acid (Tsoutsikos, et al., 2004), in one of the processes that
|
|
contribute to the accumulation of PUFA with aging.</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Animals that naturally have a
|
|
relatively low level of the highly unsaturated fats in their tissues have the greatest
|
|
longevity. For example, the naked mole rate has a life expectancy of more than 28 years, about 9
|
|
times as long as other rodents of a similar size. Only about 2% to 6% of its phospholipids
|
|
contain DHA, while about 27% to 57% of the phospholipids of mice contain DHA Mitchell, et al.,
|
|
2007). </span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>The famously long-lived people of
|
|
Azerbaijan eat a diet containing a low ratio of unsaturated to saturated fats, emphasizing
|
|
fruits, vegetables, and dairy products (Grigorov, et al., 1991).</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Some of the clearest evidence of the
|
|
protective effects of saturated fats has been published by A.A. Nanji's group, showing that they
|
|
can reverse the inflammation, necrosis, and fibrosis of alcoholic liver disease, even with
|
|
continued alcohol consumption, while fish oil and other unsaturated fats exacerbate the problem
|
|
(Nanji, et al., 2001). Glycine protects against fat accumulation in alcohol-induced liver injury
|
|
(Senthilkumar, et al., 2003), suggesting that dietary gelatin would complement the protective
|
|
effects of saturated fats.</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>The least stable n-3 fats which
|
|
accumulate with age and gradually reduce energy production also have their short term effects on
|
|
endurance. Endurance was much lower in rats fed a high n-3 fat diet, and the effect persisted
|
|
even after 6 weeks on a standard diet (Ayre and Hulbert, 1997). Analogous, but less extreme
|
|
effects are seen even in salmon, which showed increased oxidative stress on a high n-3 diet (DHA
|
|
or EPA), and lower mitochondrial cytochrome oxidase activity (Kjaer, et al., 2008). </span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Maintaining a high rate of oxidative
|
|
metabolism, without calorie restriction, retards the accumulation of PUFA, and a high metabolic
|
|
rate is associated with longevity. An adequate amount of sugar maintains both a high rate of
|
|
metabolism, and a high respiratory quotient, i.e., high production of carbon dioxide. Mole rats,
|
|
bats, and queen bees, with an unusually great longevity, are chronically exposed to high levels
|
|
of carbon dioxide. Carbon dioxide forms carbamino bonds with the amino groups of proteins,
|
|
inhibiting their reaction with the reactive "glycating" fragments of PUFA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>To minimize the accumulation of the
|
|
highly unsaturated fatty acids with aging, it's probably reasonable to reduce the amount of them
|
|
directly consumed in foods, such as fish, but since they are made in our own tissues from the
|
|
"essential fatty acids," linoleic and linolenic acids, it's more important to minimize the
|
|
consumption of those (from plants, pork, and poultry, for example).</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>In the resting state, muscles
|
|
consume mainly fats, so maintaining relatively large muscles is important for preventing the
|
|
accumulation of fats. </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"
|
|
> </span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"> <span style="font-family: Helvetica"><span><strong><h3>
|
|
REFERENCES
|
|
</h3></strong></span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Program No. 680.23. 2004 Washington,
|
|
DC: Society for Neuroscience, 2004. Online. <strong>Postmortem rat brain analysis of
|
|
phospholipid composition using P31 NMR spectroscopy, </strong>Adineh M, Kent M, Shah S,
|
|
Polelstra R, White P, Simkins R.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Eur J Pharmacol. 2003 Apr
|
|
11;466(1-2):199-205. <strong>Vascular permeabilization by intravenous arachidonate in the
|
|
rat peritoneal cavity: antagonism by antioxidants.</strong> Alvarez-Guerra M, Hannaert
|
|
P, Hider H, Chiavaroli C, Garay RP.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Aging Cell. 2006
|
|
Dec;5(6):525-32. <strong>Disparate patterns of age-related changes in lipid peroxidation in
|
|
long-lived naked mole-rats and shorter-lived mice. </strong>Andziak B, Buffenstein
|
|
R.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Lipid Mediat Cell Signal. 1994
|
|
Mar;9(2):145-53. <strong>Essential fatty acid-deficient diet modifies PAF levels in stomach
|
|
and duodenum of endotoxin-treated rats.</strong> Autore G, Cicala C, Cirino G, Maiello
|
|
FM, Mascolo N, Capasso F.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochim Biophys Acta. 1976 Nov
|
|
19;450(2):239-51. <strong>Modification of the Ehrlich ascites tumor cell nuclear
|
|
lipids.</strong> Awad AB, Spector AA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Lipids. 1997
|
|
Dec;32(12):1265-70. <strong>Dietary fatty acid profile affects endurance in rats.</strong
|
|
> Ayre KJ, Hulbert AJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Neoplasma.
|
|
1978;25(1):25-9. <strong>Neutral lipids in nuclei and chromatin fraction of young and old
|
|
Ehrlich ascites tumor cells. </strong>Balint Z, Holczinger L.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Trends Neurosci. 2004
|
|
Oct;27(10):595-600. <strong>Free radicals and aging.</strong> Barja G. "The degree of
|
|
unsaturation of tissue fatty acids also correlates inversely with maximum longevity."</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Br J Nutr. 2003
|
|
Apr;89(4):523-31. <strong>Influence of very low dietary intake of marine oil on some
|
|
functional aspects of immune cells in healthy elderly people. </strong>Bechoua S,
|
|
Dubois M, Vericel E, Chapuy P, Lagarde M, Prigent AF.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Prostaglandins Leukot Essent Fatty
|
|
Acids. 1999 May-Jun;60(5-6):393-9. <strong>Does high polyunsaturated free fatty acid level
|
|
at the feto-maternal interface alter steroid hormone message during pregnancy?</strong
|
|
> Benassayag C, Rigourd V, Mignot TM, Hassid J, Leroy MJ, Robert B, Civel C, Grange' G,
|
|
Dallot E, Tanguy J, Nunez EA, Ferre' F.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Int J Cancer. 1984 Oct
|
|
15;34(4):529-33. <strong>Effect of dietary stearic acid on the genesis of spontaneous
|
|
mammary adenocarcinomas in strain A/ST mice.</strong> Bennett AS.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Nutr Neurosci. 2010
|
|
Jun;13(3):144-50. <strong>Essential fatty acid deficiency reduces cortical spreading
|
|
depression propagation in rats: a two-generation study.</strong> Borba JM, et al.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Physiol. 2004 Dec 1;561(Pt
|
|
2):499-513. <strong>Cell swelling-induced ATP release is tightly dependent on intracellular
|
|
calcium elevations.</strong>Boudreault F, Grygorczyk R.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Breast Cancer Res Treat. 1992
|
|
Mar;20(3):185-94. <strong>Prognostic significance of tumor phosphatidylcholine stearic acid
|
|
level in breast carcinoma.</strong> Bougnoux P, <span>Chajes V, Lanson M, Hacene
|
|
K, Body G, Couet C, Le Floch O.</span></span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Nutr Health Aging.
|
|
2004;8(3):163-74. <strong>Roles of unsaturated fatty acids (especially omega-3 fatty acids)
|
|
in the brain at various ages and during ageing.</strong> Bourre JM.</span></span></span
|
|
>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochemistry (Mosc). 2010
|
|
Dec;75(12):1491-7. <strong>Dietary supplementation of old rats with hydrogenated peanut oil
|
|
restores activities of mitochondrial respiratory complexes in skeletal
|
|
muscles. </strong>Bronnikov GE, Kulagina TP, Aripovsky AV.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Proc Nutr Soc. 2008
|
|
Feb;67(1):19-27. <strong>Gender differences in the n-3 fatty acid content of
|
|
tissues. </strong>Childs CE, Romeu-Nadal M, Burdge GC, Calder PC.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Circ Shock.
|
|
1979;6(4):333-42. <strong>Resistance of essential fatty acid-deficient rats to endotoxic
|
|
shock. </strong>Cook JA, Wise WC, Callihan CS.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Cardiovasc Res. 2007 Jan
|
|
15;73(2):386-94. <strong>Dietary n-3 fatty acids promote arrhythmias during acute regional
|
|
myocardial ischemia in isolated pig hearts. </strong>Coronel R, Wilms-Schopman FJ, Den
|
|
Ruijter HM, Belterman CN, Schumacher CA, Opthof T, Hovenier R, Lemmens AG, Terpstra AH, Katan
|
|
MB, Zock P.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Int J Geriatr Psychiatry. 2003
|
|
Sep;18(Suppl 1):S23-32. <strong>The NMDA receptor antagonist memantine as a
|
|
symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical
|
|
evidence.</strong> Danysz W, Parsons CG.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Naunyn Schmiedebergs Arch Pharmacol.
|
|
2001 Nov;364(5):397-408. <strong>Aspects of the intercellular communication in aged hearts:
|
|
effects of the gap junction uncoupler palmitoleic acid.</strong> Dhein S, Hammerath
|
|
SB.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Naunyn Schmiedebergs Arch Pharmacol.
|
|
2005 Mar;371(3):202-11. <strong>Antiarrhythmic and electrophysiologicl effects of
|
|
long-chain omega-3 polyunsaturated fattty acids.</strong> Dhein S, Michaelis B, Mohr
|
|
FW.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Prostaglandins Leukot Essent Fatty
|
|
Acids. 2009 Apr;80(4):207-12. <strong>Fetal learning and memory: weak associations with the
|
|
early essential polyunsaturated fatty acid status. </strong>Dirix CE, Hornstra G,
|
|
Nijhuis JG.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Nutr. 2011
|
|
Sep;141(9):1635-42. <strong>Ingestion of (n-3) fatty acids augments basal and platelet
|
|
activating factor-induced permeability to dextran in the rat mesenteric vascular
|
|
bed. </strong>Dombrowsky H, Lautenschläger I, Zehethofer N, Lindner B, Schultz H, Uhlig
|
|
S, Frerichs I, Weiler N.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Ann Nutr Aliment.
|
|
1980;34(2):317-32. <strong>[Polyunsaturated fatty acids and aging. Lipofuscins : structure,
|
|
origin and development] </strong>[Article in French] Durand G, Desnoyers F.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Physiol. 1998 Mar 1;507 ( Pt
|
|
2):541-7. <strong>Arachidonic acid increases cerebral microvascular permeability by free
|
|
radicals in single pial microvessels of the anaesthetized rat.</strong> Easton AS,
|
|
Fraser PA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochem Mol Biol Int. 1998
|
|
Dec;46(6):1117-26. <strong>Age-related changes in plasma and tissue fatty acid composition
|
|
in Fischer 344 rats. </strong>Engler MM, Engler MB, Nguyen H.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>G Chir. 2008
|
|
Jan-Feb;29(1-2):51-7. <strong>[Traumatic shock--physiopathologic aspects]. </strong
|
|
>[Article in Italian] Fabiano G, Pezzolla A, Filograna MA, Ferrarese F.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Ann Neurol. 2006
|
|
Sep;60(3):346-55. <strong>Endogenous sex hormones, cognitive decline, and future dementia
|
|
in old men. </strong>Geerlings MI, Strozyk D, Masaki K, Remaley AT, Petrovitch H, Ross
|
|
GW, White LR, Launer LJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Am J Clin Nutr. 2004
|
|
Nov;80(5):1167-74. <strong>Docosahexaenoic acid concentrations are higher in women than in
|
|
men because of estrogenic effects.</strong> Giltay EJ, Gooren LJ, Toorians AW, Katan
|
|
MB, Zock PL.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Vopr Pitan. 1991
|
|
Mar-Apr;(2):36-40. <strong>[Characteristics of actual nutrition of the long-lived
|
|
population of Azerbaijan]</strong> [Article in Russian] Grigorov IuG, Kozlovskaia SG,
|
|
Semes'ko TM, Asadov ShA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Ann Nutr Metab.
|
|
2007;51(5):433-8. <strong>Three-year tracking of fatty acid composition of plasma
|
|
phospholipids in healthy children.</strong> Guerra A, Demmelmair H, Toschke AM,
|
|
Koletzko B.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Lab Invest. 1976
|
|
Feb;34(2):216-22. <strong>The effects of long chain free fatty acids on human neutrophil
|
|
function and structure.</strong> Hawley HP, Gordon GB.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Am J Clin Nutr. 1989
|
|
Feb;49(2):301-5. <strong>Linoleic acid and linolenic acid: effect on permeability
|
|
properties of cultured endothelial cell monolayers. </strong>Hennig B, Watkins
|
|
BA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Mol Cell Biol. 1981
|
|
Oct;1(10):939-48. <strong>Effects of free fatty acids on the organization of cytoskeletal
|
|
elements in lymphocytes.</strong> Hoover RL, Fujiwara K, Klausner RD, Bhalla DK, Tucker
|
|
R, Karnovsky MJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochim Biophys Acta. 1992 Mar
|
|
26;1113(1):71-133. <strong>Cardiolipins and biomembrane function.</strong> Hoch
|
|
FL.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Sci STKE. 2002 Sep
|
|
17;2002(150):re13. <strong>Nuclear lipid signaling. </strong>Irvine RF.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Kidney Int. 2002
|
|
Nov;62(5):1628-37. <strong>Urinary free fatty acids bound to albumin aggravate
|
|
tubulointerstitial damage. </strong>Kamijo A, Kimura K, Sugaya T, Yamanouchi M, Hase H,
|
|
Kaneko T, Hirata Y, Goto A, Fujita T, Omata M.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Prostaglandins Leukot Essent Fatty
|
|
Acids. 2002 Nov;67(5):303-8. <strong>The effect of omega-3 fatty acids on Ca-ATPase in rat
|
|
cerebral cortex.</strong>Kearns SD, Haag M.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Lipids. 2008
|
|
Sep;43(9):813-27. <strong>Dietary n-3 HUFA affects mitochondrial fatty acid beta-oxidation
|
|
capacity and susceptibility to oxidative stress in Atlantic salmon.</strong> Kjaer MA,
|
|
Todorcević M, Torstensen BE, Vegusdal A, Ruyter B.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Biol Chem. 1996 Dec
|
|
20;271(51):32722-8. <strong>Synergy by secretory phospholipase A2 and glutamate on inducing
|
|
cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal
|
|
cultures. </strong>Kolko M, DeCoster MA, de Turco EB, Bazan NG.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochem Pharmacol. 1993 Sep
|
|
1;46(5):897-904. <strong>Effects of oleoyl-CoA on the activity and functional state of
|
|
UDP-glucuronosyltransferase.</strong>Krcmery M, Zakim D.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Lipids. 1991
|
|
Jun;26(6):472-8. <strong>Study on the lipid composition of aging Fischer-344 rat lymphoid
|
|
cells: effect of long-term calorie restriction.</strong>Laganiere S, Fernandes G.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Gerontology.
|
|
1993;39(1):7-18. <strong>Modulation of membrane phospholipid fatty acid composition by age
|
|
and food restriction.</strong> Laganiere S, Yu BP.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Alzheimers Dis. 2003
|
|
Aug;5(4):315-22. <strong>Omega-3 fatty acids and risk of cognitive impairment and
|
|
dementia.</strong> Laurin D, Verreault R, Lindsay J, Dewailly E, Holub BJ.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Free Radic Biol Med. 1999
|
|
Feb;26(3-4):260-5. <strong>Modulation of cardiac mitochondrial membrane fluidity by age and
|
|
calorie intake.</strong> Lee J, Yu BP, Herlihy JT.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Lipids Health Dis. 2006 Jan
|
|
23;5:2. <strong>Selective remodeling of cardiolipin fatty acids in the aged rat
|
|
heart.</strong> Lee HJ, Mayette J, Rapoport SI, Bazinet RP.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Lipids Health Dis. 2006 Jan
|
|
23;5:2. <strong>Selective remodeling of cardiolipin fatty acids in the aged rat
|
|
heart. </strong>Lee HJ, Mayette J, Rapoport SI, Bazinet RP.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Neurosci. 2006 Jul
|
|
12;26(28):7502-12. <strong>Endogenous alpha-synuclein is induced by valproic acid through
|
|
histone deacetylase inhibition and participates in neuroprotection against glutamate-induced
|
|
excitotoxicity.</strong> Leng Y, Chuang DM.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Circ Shock. 1990
|
|
Jun;31(2):159-70. <strong>Resistance of essential fatty acid-deficient rats to
|
|
endotoxin-induced increases in vascular permeability.</strong> Li EJ, Cook JA, Spicer
|
|
KM, Wise WC, Rokach J, Halushka PV.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Drug Metab Dispos. 2002
|
|
May;30(5):531-3. <strong>Glucuronidation of the dietary fatty acids, phytanic acid and
|
|
docosahexaenoic acid, by human UDP-glucuronosyltransferases. </strong>Little JM,
|
|
Williams L, Xu J, Radominska-Pandya A.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Acta Neuropathol.
|
|
1989;78(1):16-21. <strong>Immunohistochemical localization of intracellular plasma proteins
|
|
in the human central nervous system.</strong> Liu HM, Atack JR, Rapoport SI.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Neurochem. 1984
|
|
Apr;42(4):961-8. <strong>Turnover rates of the molecular species of ethanolamine
|
|
plasmalogen of rat brain.</strong> Masuzawa Y, Sugiura T, Ishima Y, Waku K.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Psychoneuroendocrinology. 2008 Nov
|
|
27. <strong>Gender differences in rat erythrocyte and brain docosahexaenoic acid
|
|
composition: Role of ovarian hormones and dietary omega-3 fatty acid composition.</strong
|
|
> McNamara RK, Able J, Jandacek R, Rider T, Tso P.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Chromatogr B Analyt Technol Biomed
|
|
Life Sci. 2005 Nov 15;827(1):88-93. <strong>Suppression of murine cerebral F2-isoprostanes
|
|
and F4-neuroprostanes from excitotoxicity and innate immune response in vivo by alpha- or
|
|
gamma-tocopherol.</strong> Milatovic D, VanRollins M, Li K, Montine KS, Montine
|
|
TJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Exp Gerontol. 2007
|
|
Nov;42(11):1053-62. <strong>Membrane phospholipid composition may contribute to exceptional
|
|
longevity of the naked mole-rat (Heterocephalus glaber): a comparative study using shotgun
|
|
lipidomics.</strong> Mitchell TW, Buffenstein R, Hulbert AJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Pharmacol Exp Ther. 2001
|
|
Nov;299(2):638-44. <strong>Dietary saturated fatty acids reverse inflammatory and fibrotic
|
|
changes in rat liver despite continued ethanol administration.</strong> Nanji AA,
|
|
Jokelainen K, Tipoe GL, Rahemtulla A, Dannenberg AJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Ophthalmic Res.
|
|
1999;31(4):273-9. <strong>Age-related accumulation of free polyunsaturated fatty acids in
|
|
human retina.</strong> Nourooz-Zadeh J, Pereira P.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochim Biophys Acta. 2000 Aug
|
|
24;1487(1):1-14. <strong>Fish oil diet affects on oxidative senescence of red blood cells
|
|
linked to degeneration of spleen cells in mice.</strong> Oarada M, Furukawa H, Majima
|
|
T, Miyazawa T.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochem Biophys Res Commun. 2006 Jul
|
|
14;345(4):1649-56. <strong>Fatty acyl-CoA as an endogenous activator of
|
|
UDP-glucuronosyltransferases.</strong>Okamura K, Ishii Y, Ikushiro S, Mackenzie PI, Yamada
|
|
H.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Mech Ageing Dev. 2000 Jan
|
|
10;112(3):169-83. <strong>Double bond content of phospholipids and lipid peroxidation
|
|
negatively correlate with maximum longevity in the heart of mammals.</strong> Pamplona
|
|
R, Portero-Otin M, Ruiz C, Gredilla R, Herrero A, Barja G.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochim Biophys Acta 1988 Aug
|
|
17;935(1):79-86. <strong>Effect of hyperthyroidism on the transport of pyruvate in
|
|
rat-heart mitochondria.</strong> Paradies G, Ruggiero FM</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Arch Biochem Biophys 1989
|
|
Mar;269(2):595-602. <strong>Decreased activity of the pyruvate translocator and changes in
|
|
the lipid composition in heart mitochondria from hypothyroid rats.</strong> Paradies G,
|
|
Ruggiero FM</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>FEBS Lett. 1997 Apr
|
|
7;406(1-2):136-8. <strong>Age-dependent decline in the cytochrome c oxidase activity in rat
|
|
heart mitochondria: role of cardiolipin. </strong>Paradies G, Ruggiero FM, Petrosillo
|
|
G, Quagliariello E.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Eur J Biochem. 1978 Feb
|
|
1;83(1):235-43. <strong>The role of serum albumin in the uptake of fatty acids by cultured
|
|
cardiac cells from chick embryo. </strong>Paris S, Samuel D, Jacques Y, Gache C,
|
|
Franchi A, Ailhaud G.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Br J Urol. 1990
|
|
Mar;65(3):268-70. <strong>Erythrocyte stearic to oleic acid ratio in prostatic
|
|
carcinoma.</strong> Persad RA, Gillatt DA, Heinemann D, Habib NA, Smith PJ.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Atherosclerosis. 1983
|
|
Jan;46(1):21-8. <strong>Increased ratio of plasma free fatty acids to albumin during normal
|
|
aging and in patients with coronary heart disease.</strong> Pickart L.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Cell Physiol. 2010
|
|
Nov;225(3):829-36. <strong>Role of calcium and ROS in cell death induced by polyunsaturated
|
|
fatty acids in murine thymocytes.</strong> Prasad A, Bloom MS, Carpenter DO.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Nutr. 1984
|
|
Feb;114(2):255-62. <strong>The effect of essential fatty acid deficiency on basal
|
|
respiration and function of liver mitochondria in rats.</strong>Rafael J, Patzelt J,
|
|
Schäfer H, Elmadfa I.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Prostaglandins Leukot Essent Fatty
|
|
Acids. 1993 Jan;48(1):111-6. <strong>The role of free fatty acids in regulating the tissue
|
|
availability and synthesis of sex steroids.</strong> Reed MJ, Dunkley SA, Singh A,
|
|
Thomas BS, Haines AP, Cruickshank JK.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Biol Chem. 2011 Jul
|
|
29;286(30):26931-42. <strong>Unsaturated fatty acids drive disintegrin and
|
|
metalloproteinase (ADAM)-dependent cell adhesion, proliferation, and migration by modulating
|
|
membrane fluidity.</strong> Reiss K, Cornelsen I, Husmann M, Gimpl G, Bhakdi S.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Neurochem. 1982
|
|
May;38(5):1255-60. <strong>Effects of free fatty acids on synaptosomal amino acid uptake
|
|
systems. </strong>Rhoads DE, Kaplan MA, Peterson NA, Raghupathy E.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochem J. 1967
|
|
Sep;104(3):1040-7. <strong>Characterization and metabolism of ovine foetal lipids.</strong
|
|
> Scott TW, Setchell BP, Bassett JM.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Cell Death Differ. 2004 Dec;11 Suppl
|
|
2:S172-80. <strong>Water induces autocrine stimulation of tumor cell killing through ATP
|
|
release and P2 receptor binding. </strong>Selzner N, Selzner M, Graf R, Ungethuem U,
|
|
Fitz JG, Clavien PA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Pol J Pharmacol. 2003
|
|
Jul-Aug;55(4):603-11. <strong>Glycine modulates hepatic lipid accumulation in
|
|
alcohol-induced liver injury.</strong> Senthilkumar R, Viswanathan P, Nalini N.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Reprod Nutr Dev. 2005
|
|
Sep-Oct;45(5):633-46. <strong>Regulation of intracellular calcium levels by polyunsaturated
|
|
fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement
|
|
of phospholipase A2. </strong>Sergeeva M, Strokin M, Reiser G.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Neuron. 2003 Feb
|
|
20;37(4):583-95. <strong>The formation of highly soluble oligomers of alpha-synuclein is
|
|
regulated by fatty acids and enhanced in Parkinson's disease.</strong> Sharon R,
|
|
Bar-Joseph I, Frosch MP, Walsh DM, Hamilton JA, Selkoe DJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Zygote. 1993
|
|
Aug;1(3):215-23. <strong>Non-plasmalemmal localisation of the major ganglioside in sea
|
|
urchin eggs.</strong> Shogomori H, Chiba K, Kubo H, Hoshi M.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Invasion Metastasis.
|
|
1995;15(3-4):144-55. <strong>Stearate inhibits human tumor cell invasion. </strong
|
|
>Singh RK, Hardy RW, Wang MH, Williford J, Gladson CL, McDonald JM, Siegal GP.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Physiol Bohemoslov.
|
|
1990;39(2):125-34. <strong>Proportion of individual fatty acids in the non-esterified
|
|
(free) fatty acid(FFA) fraction in the serum of laboratory rats of different
|
|
ages. </strong>Smidova L, Base J, Mourek J, Cechova I.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Exp Gerontol. 2005
|
|
Apr;40(4):335-43. <strong>Unsaturated fatty acids intake and all-causes mortality: a
|
|
8.5-year follow-up of the Italian Longitudinal Study on Aging. </strong>Solfrizzi V,
|
|
D'Introno A, Colacicco AM, Capurso C, Palasciano R, Capurso S,Torres F, Capurso A, Panza
|
|
F.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Pharm Biomed Anal. 2001
|
|
Mar;24(5-6):1157-62. <strong>Bioanalysis of age-related changes of lipid metabolism in
|
|
nonagenarians.</strong> Solichova D, Juraskova B, Blaha V, Bratova M, Kusalova M,
|
|
Zdansky P, Zadak Z.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochim Biophys Acta. 1997 Apr
|
|
21;1345(3):317-26. <strong>The preferential mobilisation of C20 and C22 polyunsaturated
|
|
fatty acids from the adipose tissue of the chick embryo: potential implications regarding
|
|
the provision of essential fatty acids for neural development.</strong> Speake BK,
|
|
Cerolini S, Maldjian A, Noble RC.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Nutr. 2003
|
|
Nov;133(11):3664-9. <strong>Fish intake is positively associated with breast cancer
|
|
incidence rate. </strong>Stripp C, Overvad K, Christensen J, Thomsen BL, Olsen A,
|
|
Moller S, Tjonneland A.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Br J Pharmacol. 2003
|
|
Jul;139(5):1014-22. <strong>Docosahexaenoic acid and arachidonic acid release in rat brain
|
|
astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently
|
|
regulated by cyclic AMP and Ca2+.</strong> Strokin M, Sergeeva M, Reiser G.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Aging Clin Exp Res. 2004
|
|
Dec;16(6):425-31. <strong>Effects of dietary restriction on age-related changes in the
|
|
phospholipid fatty acid composition of various rat tissues</strong>. Tamburini I, Quartacci
|
|
MF, Izzo R, Bergamini E. "The most abundant PUFAs, 20:4(n-6) and 22:6(n-3), either remained the
|
|
same or increased with age."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Am J Physiol. 1989 Jan;256(1 Pt
|
|
1):G178-87. <strong>Saturated fatty acid diet prevents radiation-associated decline in
|
|
intestinal uptake.</strong> Thomson AB, Keelan M, Lam T, Cheeseman CI, Walker K,
|
|
Clandinin MT.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Surg Res. 2006
|
|
Sep;135(1):68-75. <strong>Inflammation effects on the electrical properties of atrial
|
|
tissue and inducibility of postoperative atrial fibrillation.</strong> Tselentakis EV,
|
|
Woodford E, Chandy J, Gaudette GR, Saltman AE.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochem Pharmacol. 2004 Jan
|
|
1;67(1):191-9. <strong>Evidence that unsaturated fatty acids are potent inhibitors of renal
|
|
UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical microsomes
|
|
and recombinant UGT1A9 and UGT2B7.</strong>Tsoutsikos P, Miners JO, Stapleton A, Thomas A,
|
|
Sallustio BC, Knights KM.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Aging Cell. 2007
|
|
Feb;6(1):15-25. <strong>N-3 polyunsaturated fatty acids impair lifespan but have no role
|
|
for metabolism.</strong> Valencak TG, Ruf T.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochim Biophys Acta. 1990 Jul
|
|
16;1045(2):128-34. <strong>Lipoproteins secreted by cultured rat hepatocytes contain the
|
|
antioxidant 1-alk-1-enyl-2-acylglycerophosphoethanolamine. </strong>Vance JE.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biol Chem. 2003 Oct
|
|
10;278(41):40020-5. <strong>Increased vesicle recycling in response to osmotic cell
|
|
swelling. Cause and consequence of hypotonicity-provoked ATP release.</strong> van der
|
|
Wijk T, Tomassen SF, Houtsmuller AB, de Jonge HR, Tilly BC.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Endocrinology. 1992
|
|
Dec;131(6):2697-702. <strong>Glutamic acid decarboxylase messenger ribonucleic acid is
|
|
regulated by estradiol and progesterone in the hippocampus. </strong>Weiland NG.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>IUBMB Life. 2008
|
|
Sep;60(9):575-90. <strong>Calcium ions in neuronal degeneration.</strong> Wojda U,
|
|
Salinska E, Kuznicki J.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Prog Clin Biol Res
|
|
1983;111:89-109. <strong>Energy metabolism in trauma and sepsis: the role of
|
|
fat. </strong>Wolfe RR, Shaw JH, Durkot MJ</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Biochem Pharmacol. 1997 Feb
|
|
21;53(4):561-70. <strong>Inhibition of UDP-glucuronosyltransferase activity by fatty
|
|
acyl-CoA. Kinetic studies and structure-activity relationship. </strong>Yamashita A,
|
|
Nagatsuka T, Watanabe M, Kondo H, Sugiura T, Waku K.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>Neurotoxicology. 2007
|
|
Nov;28(6):1220-9. <strong>Detrimental effects of post-treatment with fatty acids on brain
|
|
injury in ischemic rats.</strong> Yang DY, Pan HC, Yen YJ, Wang CC, Chuang YH, Chen SY,
|
|
Lin SY, Liao SL, Raung SL, Wu CW, Chou MC, Chiang AN, Chen CJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: Helvetica"><span>J Org Chem. 2007 Dec
|
|
7;72(25):9698-703. <strong>Asymmetric synthesis of 14-A4t-neuroprostane: hunting for a
|
|
suitable biomarker for neurodegenerative diseases.</strong> Zanoni G, Brunoldi EM,
|
|
Porta A, Vidari G. "Since isoprostanes are considered as golden standards for oxidative stress,
|
|
and due to the specificity of neuroprostanes for this condition in neurons and their relation
|
|
with Alzheimer's and Parkinson's diseases, they are envisioned to be suitable biomarkers for
|
|
these pathologies."</span></span></span>
|
|
</blockquote>
|
|
<p> </p>
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