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

. 2017 Mar;25(3):561-571.

doi: 10.1002/oby.21757. Epub 2017 Feb 1.

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

Renlong Li et al. Obesity (Silver Spring). 2017 Mar.

Abstract

Objective: 1,25(OH)2 D3 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 D3 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 D3 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 D3 . 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 D3 diminished HFD-induced liver damage and steatosis, changes accompanied by autophagy and ATG16L1 expression upregulation. Inhibition of 1,25(OH)2 D3 -induced autophagy mediated by 3-MA blocked the protective effects of 1,25(OH)2 D3 on hepatic steatosis. Additionally, 1,25(OH)2 D3 -induced autophagy appeared to play a role in anti-inflammation and lipid metabolism modulation in the liver. In HepG2 cells, 1,25(OH)2 D3 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 D3 -mediated autophagy against lipid accumulation were abolished by 3-MA. Furthermore, siRNA-mediated ATG16L1 knockdown prevented 1,25(OH)2 D3 -induced autophagy, resulting in increased fat accumulation.

Conclusions: The data suggest that 1,25(OH)2 D3 may ameliorate hepatic steatosis by inducing autophagy by upregulating ATG16L1.

© 2017 The Obesity Society.

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