1,25(OH)2D3 attenuates hepatic steatosis by inducing autophagy in mice

作者：Renlong Li, Enshuang Guo, Jiankun Yang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang · 发表于：Obesity · 年份：2017 · DOI：10.1002/oby.21757 · 被引用次数：87 · 研究领域：Autophagy in Disease and Therapy、MicroRNA in disease regulation、Ginger and Zingiberaceae research

Objective 1,25(OH)2D3 has been reported to attenuate liver steatosis; however, its exact mechanism of action remains poorly understood. This study aimed to determine whether 1,25(OH)2D3 can attenuate hepatic steatosis by inducing autophagy. Methods Male C57BL/6 mice fed a high‐fat diet (HFD) were injected with 1,25(OH)2D3 for 4 weeks. These mice were given 3‐methyladenine (3‐MA) to inhibit autophagy. HepG2 cells were preincubated with a free fatty acid (FFA) and then treated with 1,25(OH)2D3. Vitamin D receptor (VDR) shRNA and autophagy‐related 16‐like 1 (ATG16L1) siRNA were used for VDR knockdown or ATG16L1 silencing, respectively. Results 1,25(OH)2D3 diminished HFD‐induced liver damage and steatosis, changes accompanied by autophagy and ATG16L1 expression upregulation. Inhibition of 1,25(OH)2D3‐induced autophagy mediated by 3‐MA blocked the protective effects of 1,25(OH)2D3 on hepatic steatosis. Additionally, 1,25(OH)2D3‐induced autophagy appeared to play a role in anti‐inflammation and lipid metabolism modulation in the liver. In HepG2 cells, 1,25(OH)2D3 reduced lipid accumulation and increased autophagy and ATG16L1 expression; however, this effect was abrogated after VDR knockdown. The protective effects of 1,25(OH)2D3‐mediated autophagy against lipid accumulation were abolished by 3‐MA. Furthermore, siRNA‐mediated ATG16L1 knockdown prevented 1,25(OH)2D3‐induced autophagy, resulting in increased fat accumulation. Conclusions The data suggest that 1,25(OH)2D3 may ameliorat...