Transgenic SND1 Ameliorates HFD-induced Hepatic Steatosis And Insulin Resistance

Background & Aims: Muti-functional protein SND1 transcriptionally activates adipogenesis and regulates adipocyte differentiation, but its contribution to the metabolicsyndromein vivo is unclear. This study was designed to examine the impact of global SND1 overexpression in vivoin the high-fat diet-induced(HFD)nonalcoholic fatty liver disease(NAFLD).Methods:SND1 global overexpression mice(SND1-Tg)and wild type controls were studied forchanges in liver and white adipose histology and metabolic phenotype at baseline(normal-chow diet) and after time course of 12 weeks feeding with a 60% high-fat diet starting at 8 weeks of age. In additional experiments, microarray analyses on liver wereperformedfollow by various RT-PCR verifications.Results: SND1 transgenic micewas revealed a previously unrecognized yet important role in the program of activation in the pathway of hepatic cholesterol and phospholipids biosynthesis and de novolipogenesisin white adipose tissue in HFD-induced NAFLD, accompanied byreducedtriglyceride accumulation and more systemic insulin sensitivity.More importantly, HFD-transgenic miceshow reduced hepatic steatosis, to a large extent due to the increased level of circulating leptin derived from white adipose and high output of low density lipoprotein-cholesterol from liver via the potential mechanism of facilitating SREBP2 nuclear translocation. This work suggests SND1 transgene can improve hepatic steatosis and insulin resistance in nonalcoholic fatty liver disease.Conclusions:SND1transgene in obesity mice can ameliorate diet-induced hepatic steatosisand insulin resistance.