Nestlé Research, Société des Produits Nestlé, CH-1015 Lausanne, Switzerland.
Department of Pharmacology and Toxicology, University of Lausanne, CH-1011 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2200083119. doi: 10.1073/pnas.2200083119. Epub 2022 Mar 1.
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.
意义
虽然越来越多的证据表明，昼夜节律紊乱与肥胖症、2 型糖尿病和非酒精性脂肪性肝病（NAFLD）等病理状况有关，但相关机制仍描述不清。在这里，我们发现，在人类和小鼠中，NAFLD 的发病机制与昼夜节律钟的破坏以及生长激素和性激素途径的紊乱有关。然而，尽管这种情况可以保护小鼠免受纤维化和胰岛素抵抗的发展，但它与人类纤维化的增加相关。这表明，昼夜节律钟的紊乱及其相关的生长激素和性激素途径的破坏，对代谢和肝脏疾病的发病机制至关重要。
