Divergent Role of Estrogen-Related Receptor α in Lipid- and Fasting-Induced Hepatic Steatosis in Mice.

摘要: Given the increasing prevalence of obesity and metabolic syndrome, identification intrinsic molecular programs responsible for ensuring fuel homeostasis preventing disease is needed. We investigated whether orphan nuclear receptor estrogen-related α (ERRα), a major regulator energy metabolism, plays role in lipid development nonalcoholic fatty liver (NAFLD) response to chronic high-fat diet (HFD) consumption long-term fasting. Systemic ablation ERRα mice demonstrated clear beneficial effects loss function protection from HFD-provoked body weight gain manifested not only reduction white adipose tissue stores but also an impediment intrahepatic accumulation. The prevention HFD-induced NAFLD ERRα-null was underscored by transcriptional repression de novo lipogenesis, which upregulated wild-type mice, known contributing factor lipid-stimulated hepatic steatosis. Surprisingly, given these findings, deficiency had no significant impact on degree fasting-induced NAFLD, involving mobilization adipocyte triglyceride (TG) into liver. However, presence essential acute refeeding-mediated reversal TG accretion, underpinned impaired downregulation lipolysis reduced mitochondrial oxidative activity. Taken together, regulation handling depended nutritional state, suggesting that negative modulation activity could be envisaged prevent lipid-induced whereas inducing its would useful treat reverse instilled disease.