Liraglutide ameliorates hepatic steatosis via retinoic acid receptor ‐related orphan receptor α‐mediated autophagy pathway

AbstractLiraglutide, an analog of human glucagon-like peptide-1 (GLP-1), has been found to improve hepatic steatosis in clinical practice. However, the underlying mechanism remains to be fully defined. Increasing evidence suggests that retinoic acid receptor-related orphan receptor α (RORα) is involved in hepatic lipid accumulation. In the current study, we investigated whether the ameliorating impact of liraglutide on lipid-induced hepatic steatosis is dependent on RORα activity and examined the underlying mechanisms. Cre-loxP-mediated, liver-specificRor α knockout (Rora LKO) mice, and littermate controls with aRoraloxp/loxp genotype were established. The effects of liraglutide on lipid accumulation were evaluated in mice challenged with a high-fat diet (HFD) for 12  weeks. Moreover, mouse AML12 hepatocytes expressing small interfering RNA (siRNA) ofRora were exposed to palmitic acid to explore the pharmacological mechanism of liraglutide. The results showed that liraglutide treatment significantly alleviated HFD-induced liver steatosis, marked by reduced liver weight and triglyceride accumulation, improved glucose tolerance and serum levels of lipid profiles and aminotransferase. Consistently, liraglutide also ameliorated lipid deposits in a steatotic hepatocyte model in vitro. In addition, liraglutide treatment reversed the HFD-induced downregulation ofRora expression and autophagic activity in mouse liver tissues. However, the beneficial effect of liraglutide on hep...
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH ARTICLE Source Type: research