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1,25(OH) 2 D 3 attenuates hepatic steatosis by inducing autophagy in mice
Author(s) -
Li Renlong,
Guo Enshuang,
Yang Jiankun,
Li Anyi,
Yang Yan,
Liu Shenpei,
Liu Anding,
Jiang Xiaojing
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21757
Subject(s) - autophagy , steatosis , atg16l1 , gene knockdown , downregulation and upregulation , chemistry , endocrinology , calcitriol receptor , medicine , gene silencing , vitamin d and neurology , biochemistry , apoptosis , gene
Objective 1,25(OH) 2 D 3 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) 2 D 3 can attenuate hepatic steatosis by inducing autophagy. Methods Male C57BL/6 mice fed a high‐fat diet (HFD) were injected with 1,25(OH) 2 D 3 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) 2 D 3 . 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) 2 D 3 diminished HFD‐induced liver damage and steatosis, changes accompanied by autophagy and ATG16L1 expression upregulation. Inhibition of 1,25(OH) 2 D 3 ‐induced autophagy mediated by 3‐MA blocked the protective effects of 1,25(OH) 2 D 3 on hepatic steatosis. Additionally, 1,25(OH) 2 D 3 ‐induced autophagy appeared to play a role in anti‐inflammation and lipid metabolism modulation in the liver. In HepG2 cells, 1,25(OH) 2 D 3 reduced lipid accumulation and increased autophagy and ATG16L1 expression; however, this effect was abrogated after VDR knockdown. The protective effects of 1,25(OH) 2 D 3 ‐mediated autophagy against lipid accumulation were abolished by 3‐MA. Furthermore, siRNA‐mediated ATG16L1 knockdown prevented 1,25(OH) 2 D 3 ‐induced autophagy, resulting in increased fat accumulation. Conclusions The data suggest that 1,25(OH) 2 D 3 may ameliorate hepatic steatosis by inducing autophagy by upregulating ATG16L1.