Renlong Li1,2, Enshuang Guo1,2, Jiankun Yang3, Anyi Li4, Yan Yang3, Shenpei Liu3, Anding Liu3, Xiaojing Jiang1,2. 1. Graduate School, Southern Medical University, Guangzhou, China. 2. Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China. 3. Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Animal Experimental Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.
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.
Authors: Ana Blas-García; Nadezda Apostolova; Federico Lucantoni; Ana M Benedicto; Aleksandra Gruevska; Ángela B Moragrega; Isabel Fuster-Martínez; Juan V Esplugues Journal: Cell Death Dis Date: 2022-04-20 Impact factor: 9.685
Authors: Krisztina Lajtai; Csilla Terézia Nagy; Róbert Tarszabó; Rita Benkő; Leila Hadjadj; Réka Eszter Sziva; Dóra Gerszi; Bálint Bányai; Péter Ferdinandy; György László Nádasy; Zoltán Giricz; Eszter Mária Horváth; Szabolcs Várbíró Journal: Biomolecules Date: 2019-09-10