Mammalian sirtuin 1 is involved in the protective action of dietary saturated fat against alcoholic fatty liver in mice.
This study was undertaken to elucidate the mechanism underlying the protective effect of a high saturated fat (HSF) diet against the development of alcoholic fatty liver in mice. We tested the effects of a HSF diet on the ethanol-mediated increase in hepatic sterol regulatory element binding protein 1 (SREBP-1) activity. Thirty-two male mice were divided into 4 groups and fed liquid diets consisting of either a high polyunsaturated fat (40% of energy from corn oil) or a HSF (40% of energy from cocoa butter) diet with or without ethanol for 4 wk. In the ethanol-containing diets, ethanol was substituted for an equivalent amount of carbohydrate to provide 27.5% of the total energy. Control mice were pair-fed the same volume of liquid diets as the ethanol-fed mice. The HSF diet suppressed the increase in mature SREBP-1 protein and prevented increased mRNA of the SREBP-1-regulated lipogenic enzymes in the ethanol-fed mice (P < 0.05). Sirtuins 1 (SIRT1), a NAD+-dependent class III histone deacetylase, was upregulated by ethanol administration in mice fed the HSF diet (P < 0.05). The HSF diet blocked histone H3 at lysine 9 (lys9) hyperacetylation and attenuated association of acetylated histone H3-Lys9 with the promoters of mitochondrial glycerol-3-phosphate acyltransferase and stearoyl-CoA desaturase 1 in the livers of the ethanol-fed mice. These results suggest that the protective effects of HSF diet against the development of alcoholic liver steatosis may occur via regulation of the hepatic SIRT1-SREBP-1-histone H3 axis, suppressing the expression of genes encoding lipogenic enzymes and slowing the synthesis of hepatic fatty acids.
You
Min
M
Department of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, FL 33612, USA. myou@health.usf.edu
Cao
Qi
Q
Liang
Xiaomei
X
Ajmo
Joanne M
JM
Ness
Gene C
GC
D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D005227:Fatty Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005235:Fatty Liver, Alcoholic / Q000378:metabolism / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D006657:Histones; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D000431:Ethanol; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins