ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism.
ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism.
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DOI：
10.1016/j.celrep.2017.03.026
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发表时间：
2017-04-04
期刊：
影响因子：
8.8
通讯作者：
Mashek DG
中科院分区：
文献类型：
--
作者：
Sathyanarayan A;Mashek MT;Mashek DG
肝脂滴（LD）分解代谢被认为是通过脂质脂肪酶如脂肪甘油三酯脂肪酶（ATGL）或脂滴自噬发生的，这一过程被称为脂噬。我们测试了这些代谢过程之间的潜在相互作用及其对肝脂质代谢的影响。我们发现肝脏ATGL是诱导自噬和脂噬的必要和充分条件。此外，ATGL需要脂噬来促进LD分解代谢和随后水解脂肪酸（FAs）的氧化。先前的研究表明ATGL促进SIRT1 （SIRT1）活性，在肝脏特异性SIRT1 - / -小鼠和原代肝细胞中的研究表明，SIRT1是ATGL介导的自噬和脂噬诱导所必需的。综上所述，这些研究表明atgl介导的信号通过SIRT1促进自噬/脂噬，作为控制肝脏LD分解代谢和FA氧化的主要手段。
Hepatic lipid droplet (LD) catabolism is thought to occur via cytosolic lipases such as adipose triglyceride lipase (ATGL) or through autophagy of LDs, a process known as lipophagy. We tested the potential interplay between these metabolic processes and its effects on hepatic lipid metabolism. We show that hepatic ATGL is both necessary and sufficient to induce both autophagy and lipophagy. Moreover, lipophagy is required for ATGL to promote LD catabolism and the subsequent oxidation of hydrolyzed fatty acids (FAs). Following previous work showing that ATGL promotes sirtuin 1 (SIRT1) activity, studies in liver-specific SIRT1−/− mice and in primary hepatocytes reveal that SIRT1 is required for ATGL-mediated induction of autophagy and lipophagy. Taken together, these studies show that ATGL-mediated signaling via SIRT1 promotes autophagy/lipophagy as a primary means to control hepatic LD catabolism and FA oxidation.