Prosteatotic genes are associated with unsaturated fat suppression of saturated fat-induced hepatic steatosis in C57BL/6 mice.
Both high sugar and fat diets can induce prosteatotic genes, leading to obesity and obesity-associated diseases, including hepatic steatosis. Unsaturated fat/fatty acid (USFA) reduces high sugar-induced hepatic steatosis by inhibiting the induced prosteatotic genes. In contrast, it is still unclear how USFA ameliorates saturated fat/fatty acid (SFA)-induced hepatic steatosis. As sugar and fat have different transport and metabolic pathways, we hypothesized that USFA suppressed SFA-induced hepatic steatosis via a different set of prosteatotic genes. To test this, we implemented high SFA vs USFA diets and a control diet in C57BL/6 mice for 16 weeks. Severe hepatic steatosis was induced in mice fed the SFA diet. Among a nearly complete set of prosteatotic genes, only the stearoyl-coenzyme a desaturase 1 (Scd1), cluster of differentiation 36 (Cd36), and peroxisome proliferator-activated receptor γ (Pparγ) genes that were differentially expressed in the liver could contribute to SFA-induced steatosis or the alleviative effect of USFA. That is, the SFA diet induced the expression of Cd36 and Pparγ but not Scd1, and the USFA diet suppressed Scd1 expression and the induction of Cd36 and Pparγ. These findings were mainly recapitulated in cultured hepatocytes. The essential roles of SCD1 and CD36 were confirmed by the observation that the suppression of SCD1 and CD36 with small interfering RNA or drug treatment ameliorated SFA-induced lipid accumulation in hepatocytes. We thus concluded that SCD1, CD36, and PPARγ were essential to the suppression of SFA-induced hepatic steatosis by main dietary USFA, which may provide different therapeutic targets for reducing high-fat vs sugar-induced hepatic steatosis.
Institute of Epigenetics and Epigenomics, Yangzhou University, 48 Wenhui East Road, Yangzhou, Jiangsu 225009, China; College of Animal Science and Technology, Yangzhou University, 48 Wenhui East Road, Yangzhou, Jiangsu 225009, China; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA. Electronic address: tygeng@yzu.edu.cn.
Tuoyu
T
Geng
College of Animal Science and Technology, Yangzhou University, 48 Wenhui East Road, Yangzhou, Jiangsu 225009, China.
Lili
L
Xia
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA.
Sarah
S
Russo
Union Hospital of Cecil County, 106 Bow St, Elkton, MD 21921, USA.
Davida
D
Kamara
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA; Ralph H Johnson Veteran's Affairs Medical Center, 109 Bee St, 29403, Charleston, SC, USA.
Lauren Ashley
LA
Cowart
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D005227:Fatty Acids / Q000009:adverse effects* / Q000494:pharmacology; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D015870:Gene Expression; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism
D018955:CD36 Antigens; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D047495:PPAR gamma; D013230:Stearoyl-CoA Desaturase
Hepatic cells; Hepatic steatosis; Obese mice; Saturated fatty acid; Unsaturated fatty acid