Vitamin D 1,25-Dihydroxyvitamin D_(3) reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization  

作　　者：Wen-Jing Luo Xian-Wen Dong Hua Ye Qiao-Su Zhao Qiu-Bo Zhang Wen-Ying Guo Hui-Wei Liu Feng Xu 

机构地区：[1]Department of Gastroenterology,Ningbo Medical Center Lihuili Hospital,Ningbo 315000,Zhejiang Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第12期4685-4699,共15页世界胃肠肿瘤学杂志（英文）

基　　金：Supported by the Natural Science Foundation of Ningbo,No.202003N4234;and Medical and Health Research Project of Zhejiang Province,No.2024KY1477.

摘　　要：BACKGROUND Non-alcoholic fatty liver disease(NAFLD),which is a significant liver condition associated with metabolic syndrome,is the leading cause of liver diseases globally and its prevalence is on the rise in most nations.The protective impact of vitamin D on NAFLD and its specific mechanism remains unclear.AIM To examine the role of vitamin D in NAFLD and how vitamin D affects the polarization of hepatic macrophages in NAFLD through the vitamin D receptor(VDR)-peroxisome proliferator activated receptor(PPAR)γpathway.METHODS Wild-type C57BL/6 mice were provided with a high-fat diet to trigger NAFLD model and administered 1,25-dihydroxy-vitamin D[1,25(OH)_(2)D_(3)]supplementation.1,25(OH)_(2)D_(3) was given to RAW264.7 macrophages that had been treated with lipid,and a co-culture with AML12 hepatocytes was set up.Lipid accumulation,lipid metabolism enzymes,M1/M2 phenotype markers,proinflammatory cytokines and VDR-PPARγpathway were determined.RESULTS Supplementation with 1,25(OH)_(2)D_(3) relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD.Administration of 1,25(OH)_(2)D_(3) suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids,thereby directly relieving lipid accumulation and metabolism in hepatocytes.The VDR-PPARγpathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)_(2)D_(3).CONCLUSION Supplementation with 1,25(OH)_(2)D_(3) improved hepatic steatosis and lipid metabolism in NAFLD,linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages,partially by regulating the VDRPPARγpathway.The involvement of 1,25(OH)_(2)D_(3) in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.

关 键 词：Non-alcoholic fatty liver disease HEPATOCYTES MACROPHAGES Polarization Vitamin D receptor Peroxisome proliferator activated receptorγ 

分 类 号：R735.7[医药卫生—肿瘤]