Prosteatotic genes are associated with unsaturated fat suppression of saturated fat-induced hepatic steatosis in C57BL/6 mice

Abstract

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.

High-Fat Diet Feeding Alters Expression of Hepatic Drug-Metabolizing Enzymes in Mice

“…2A). Although this is consistent with previous reports (Kim et al, 2004;Kudo et al, 2009;Geng et al, 2015), others have reported decreased hepatic Cyp3a11 expression or activity upon HFD feeding in mice (Yoshinari et al, 2006;Ghose et al, 2011;Wahlang et al, 2014). Differences in diet composition and housing condition may have contributed to the discrepancy.…”

SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes

“…A recent study from our laboratory demonstrated that dietary fat composition (i.e., saturated vs. unsaturated) had a profound effect on deleterious liver outcomes, including ER stress, liver weight, and hepatic steatosis, which are components of NAFLD ( 22,(26)(27)(28)(29)(30). Moreover, other studies in our laboratory and others indicated that palmitate (C16:0), but not oleate (C18:1), increased expression of SphK1 in skeletal muscle, and that the enzyme was required for expression of proinfl ammatory genes in primary skeletal muscle cells and also in skeletal muscle in mice on a highfat diet ( 7,13 ).…”

Prosteatotic and Protective Components in a Unique Model of Fatty Liver: Gut Microbiota and Suppressed Complement System

“…The protocol for immunoblot analysis was also previously described60. The following antibodies were used in this study: Complement C5 (Cat.…”