研究人员发现，通过敲减锌指蛋白423（ZFP423）来遗传增强脂肪细胞的生热作用，会通过增加小鼠无效的肌酸循环来减弱在非活动期（光照期）食用高脂肪饮食引起的肥胖。脂肪细胞肌酸代谢的昼夜控制是饮食诱导的产热时间的基础，通过过表达节律激活剂BMAL1（brain and muscle Arnt-like protein-1）可增强脂肪细胞的昼夜节律，并改善饮食诱导的肥胖期间的代谢并发症。这些发现揭示了有节律的肌酸介导的产热是一种基本机制，在限制时间的饮食过程中驱动代谢益处。
据介绍，摄食节律与光-暗周期不一致，导致外周昼夜钟紊乱和肥胖。相反，将进食限制在活动期可通过尚不清楚的机制缓解代谢综合征。
附：英文原文
Title: Time-restricted feeding mitigates obesity through adipocyte thermogenesis
Author: Chelsea Hepler, Benjamin J. Weidemann, Nathan J. Waldeck, Biliana Marcheva, Jonathan Cedernaes, Anneke K. Thorne, Yumiko Kobayashi, Rino Nozawa, Marsha V. Newman, Peng Gao, Mengle Shao, Kathryn M. Ramsey, Rana K. Gupta, Joseph Bass
Issue&Volume: 2022-10-21
Abstract: Misalignment of feeding rhythms with the light-dark cycle leads to disrupted peripheral circadian clocks and obesity. Conversely, restricting feeding to the active period mitigates metabolic syndrome through mechanisms that remain unknown. We found that genetic enhancement of adipocyte thermogenesis through ablation of the zinc finger protein 423 (ZFP423) attenuated obesity caused by consumption of a high-fat diet during the inactive (light) period by increasing futile creatine cycling in mice. Circadian control of adipocyte creatine metabolism underlies the timing of diet-induced thermogenesis, and enhancement of adipocyte circadian rhythms through overexpression of the clock activator brain and muscle Arnt-like protein-1 (BMAL1) ameliorated metabolic complications during diet-induced obesity. These findings uncover rhythmic creatine-mediated thermogenesis as an essential mechanism that drives metabolic benefits during time-restricted feeding.
DOI: abl8007
Source: https://www.science.org/doi/10.1126/science.abl8007