Proceedings of the National Academy of Sciences of the United States of America · 2022
Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease.
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Jouffe Céline, Weger Benjamin D, Martin Eva, Atger Florian, Weger Meltem, Gobet Cédric, Ramnath Divya, Charpagne Aline, Morin-Rivron Delphine, Powell Elizabeth E, Sweet Matthew J, Masoodi Mojgan, Uhlenhaut N Henriette, Gachon Frédéric
Аннотация
SignificanceWhile increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases.