Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids.
OBJECTIVE
We reported that reduced dietary intake of polyunsaturated fatty acids (PUFA) such as arachidonic (AA,20:4n6,omega-6) and docosahexaenoic (DHA,22:6n3,omega-3) acids led to alcohol-induced fatty liver and fibrosis. This study was aimed at studying the mechanisms by which a DHA/AA-supplemented diet prevents alcohol-induced fatty liver.


METHODS
Male Long-Evans rats were fed an ethanol or control liquid-diet with or without DHA/AA for 9 weeks. Plasma transaminase levels, liver histology, oxidative/nitrosative stress markers, and activities of oxidatively-modified mitochondrial proteins were evaluated.


RESULTS
Chronic alcohol administration increased the degree of fatty liver but fatty liver decreased significantly in rats fed the alcohol-DHA/AA-supplemented diet. Alcohol exposure increased oxidative/nitrosative stress with elevated levels of ethanol-inducible CYP2E1, nitric oxide synthase, nitrite and mitochondrial hydrogen peroxide. However, these increments were normalized in rats fed the alcohol-DHA/AA-supplemented diet. The number of oxidatively-modified mitochondrial proteins was markedly increased following alcohol exposure but significantly reduced in rats fed the alcohol-DHA/AA-supplemented diet. The suppressed activities of mitochondrial aldehyde dehydrogenase, ATP synthase, and 3-ketoacyl-CoA thiolase in ethanol-exposed rats were also recovered in animals fed the ethanol-DHA/AA-supplemented diet.


CONCLUSIONS
Addition of DHA/AA prevents alcohol-induced fatty liver and mitochondrial dysfunction in an animal model by protecting various mitochondrial enzymes most likely through reducing oxidative/nitrosative stress.
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rm 2S-30, Bethesda, MD 20892-9410, USA. bjs@mail.nih.gov
Byoung-Joon
BJ
Song
Kwan-Hoon
KH
Moon
Nils U
NU
Olsson
Norman
N
Salem
D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005235:Fatty Liver, Alcoholic / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D028361:Mitochondrial Diseases / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D020318:Rats, Long-Evans; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D002492:Central Nervous System Depressants; D004042:Dietary Fats, Unsaturated; D005231:Fatty Acids, Unsaturated; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D019001:Nitric Oxide Synthase