Li Hongqiang, Sun Jian, Li Bojiang, Jiang Aiwen, Tao Jingli, Ning Caibo, Li Rongyang, Liu Honglin
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, China.
Front Nutr. 2022 Jul 4;9:917801. doi: 10.3389/fnut.2022.917801. eCollection 2022.
Intermittent fasting is one of the most common clinical treatments for the obesity, a main risk factor of the metabolic syndrome which can lead to a variety of diseases. Fasting-induced fat mobilization alters the metabolic state of lipid in the liver, predisposing to increase the hepatic lipid droplet aggregation and triglyceride levels. However, the underlying mechanisms regarding the lipid droplet aggregation in the liver after fasting remains elusive. Here, we report that a lipid droplet surface binding protein Cidec (cell death inducing DFFA like effector C) is activated by AMPK to regulate the hepatic lipid droplet fusion following fasting in obese mice. Specifically, we found that lipid droplets were significantly aggregated in the liver of high-fat-diet and mice after 16 and 24 h of fasting, accompanied by the dramatically up-regulated expression of . Consistently, overexpression of in the AML12 cells resulted in the intracellular lipid droplet aggregation. Furthermore, we showed that fasting caused the up-regulated expression of AMPK, which in turn activated the transcription of through the transcription factor PPARγ. Altogether, our observations reveal that fasting-induced hepatic lipid droplet aggregation is mediated by the AMPK-activated expression of via PPARγ, extending our understanding about the molecular mechanism of the impact of fasting on the obesity and providing potential targets for the treatment of human obesity.
间歇性禁食是治疗肥胖症最常见的临床方法之一，肥胖症是代谢综合征的主要危险因素，可导致多种疾病。禁食诱导的脂肪动员改变了肝脏中脂质的代谢状态，易导致肝脏脂质滴聚集和甘油三酯水平升高。然而，禁食后肝脏中脂质滴聚集的潜在机制仍不清楚。在此，我们报道脂质滴表面结合蛋白Cidec（细胞死亡诱导DFFA样效应因子C）在肥胖小鼠禁食后被AMPK激活，以调节肝脏脂质滴融合。具体而言，我们发现高脂饮食小鼠在禁食16小时和24小时后，肝脏中的脂质滴明显聚集，同时伴随着Cidec的显著上调表达。同样，在AML12细胞中过表达Cidec导致细胞内脂质滴聚集。此外，我们表明禁食导致AMPK表达上调，进而通过转录因子PPARγ激活Cidec的转录。总之，我们的观察结果揭示，禁食诱导的肝脏脂质滴聚集是由AMPK通过PPARγ激活Cidec的表达介导的，扩展了我们对禁食对肥胖影响的分子机制的理解，并为人类肥胖症的治疗提供了潜在靶点。
