Affiliation:
1. Huashan Hospital of Fudan University
Abstract
Abstract
Background and Aims: Obesity and non-alcoholic fatty liver disease (NAFLD) are major health concerns. The circadian rhythm is an autonomous and intrinsic timekeeping system closely associated with energy metabolism and obesity. Thus, this study explored the role of brain and muscle aryl hydrocarbon receptor nuclear translocator-like1 (BMAL1), a circadian clock regulator, in the development of obesity and NAFLD.Methods We generated BMAL1 knockout (BMAL1 KO) mice to imitate circadian rhythm disruption. The study comprised three groups from the same litter: BMAL1 KO mice fed a high-fat diet (to establish obesity and NAFLD phenotypes), wild-type mice fed normal chow, and wild-type mice fed a high-fat diet. The metabolic and NAFLD phenotypes were assessed via physiological measurements and histological examinations. Quantitative polymerase chain reaction and western blotting were used to identify and validate changes in the signaling pathways responsible for the altered NAFLD phenotypes in the wild-type and BMAL1 KO mice.Results BMAL1 depletion protected against obesity and metabolic disorders induced by a high-fat diet. BMAL1 deficiency also relieved hepatic steatosis and decreased cluster of differentiation 36 and peroxisome proliferator-activated receptor gamma (i.e., PPARγ) expression.Conclusion BMAL1 plays an important role in the development of obesity and NAFLD and, thus, is a potential therapeutic target for these conditions.
Publisher
Research Square Platform LLC
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