title: 1,25(OH)2D3attenuates hepatic steatosis by inducing autophagy in mice.
abstract: 1,25(OH)2D3has been reported to attenuate liver steatosis; however, its exact mechanism of action remains poorly understood. This study aimed to determine whether 1,25(OH)2D3can attenuate hepatic steatosis by inducing autophagy.
  
  
  
  Male C57BL/6 mice fed a high-fat diet (HFD) were injected with 1,25(OH)2D3for 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.
  
  
  
  1,25(OH)2D3diminished 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)2D3on 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)2D3reduced 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.
  
  
  
  The data suggest that 1,25(OH)2D3may ameliorate hepatic steatosis by inducing autophagy by upregulating ATG16L1.
authors.affiliation: Graduate School, Southern Medical University, Guangzhou, China.|Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Renlong
authors.initials: R
authors.lastname: Li
authors.affiliation: Graduate School, Southern Medical University, Guangzhou, China.|Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Enshuang
authors.initials: E
authors.lastname: Guo
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Animal Experimental Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Anyi
authors.initials: A
authors.lastname: Li
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shenpei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
authors.affiliation: Graduate School, Southern Medical University, Guangzhou, China.|Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000071183:Autophagy-Related Proteins; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; C025946:3-methyladenine; D002117:Calcitriol; D000225:Adenine