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 Printable version |
Regulation by diet and liver of brain metabolism of nutritionally essential polyunsaturated fatty acids |
Oléagineux, Corps Gras, Lipides. Volume 14, Number 3, 216-23, Mai-Août 2007, Conférence Chevreul
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 Free Article
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Author(s) : Stanley I Rapoport, Jagadeesh S Rao, Miki Igarashi |
Summary : It is possible to inject radiolabeled polyunsaturated fatty acids (PUFAs) intravenously to quantify rates of brain and liver PUFA metabolism in the intact organism, in relation to diet, aging or disease. Because circulating α-linolenic acid (α-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6) in plasma do not contribute to brain docosahexaenoic acid (DHA, 22:6n-3) or arachidonic acid (AA, 20:4n-6), respectively, and DHA and AA cannot be synthesized de novo in vertebrate tissue, rates of incorporation of circulating DHA or AA into brain provide exact measurements of their rates of consumption by brain. Using positron emission tomography imaging, we reported that the adult human brain consumes AA and DHA at rates of 17.8 and 4.6 mg/day, respectively, and that the rate of AA consumption doesn’t change with age. In unanesthetized adult rats fed an n-3 PUFA “adequate” diet containing 4.6% (of total fatty acids) α-LNA as its only n-3 PUFA, the liver secretes DHA derived from circulating α-LNA ten-times faster than the brain consumes DHA\; thus the liver is capable of supplying all the brain’s DHA. With a low dietary α-LNA level, rat liver coefficients of α-LNA conversion to DHA are increased because of increased liver elongase and desaturase activities, and DHA loss from brain is slowed due to downregulated DHA-metabolizing enzymes, including Ca
2+-independent phospholipase A
2 (iPLA
2). The n-3 PUFA “deficient” diet also increases brain expression of AA-metabolizing enzymes, cytosolic cPLA
2, secretory sPLA
2 and cyclooxygenase-2, and the brain docosapentaenoic acid (22:5n-6) concentration. These changes, plus reduced expression of brain derived neurotrophic factor (BDNF) caused by the “deficient” diet, likely increase brain vulnerability to excitotoxicity and inflammation. |
Keywords : docosahexaenoic acid, liver, brain, rat, n-3 PUFAs, imaging, metabolism, phospholipase A
2, BDNF, diet, arachidonic acid |
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