Abstract
Objectives
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 depletion also prevented hepatic steatosis and inhibited cluster of differentiation 36 and peroxisome proliferator-activated receptor gamma (i.e., PPARĪ³) expression.
Conclusions
BMAL1 plays an important role in the development of obesity and NAFLD and, thus, is a potential therapeutic target for these conditions.
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Data availability
Data will be made available on request.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (grant numbers 81800751, 81970458, and 82100882).
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WL and QS conceived, designed, and supervised the study. CZ, HC, BX, YS, QY and RH conducted the study and analyzed the results. CZ and ZZ wrote and revised the manuscript. QS provided financial support.
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Zhan, C., Chen, H., Zhang, Z. et al. BMAL1 deletion protects against obesity and non-alcoholic fatty liver disease induced by a high-fat diet. Int J Obes 48, 469ā476 (2024). https://doi.org/10.1038/s41366-023-01435-w
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DOI: https://doi.org/10.1038/s41366-023-01435-w