Luo Wen-Jing, Dong Xian-Wen, Ye Hua, Zhao Qiao-Su, Zhang Qiu-Bo, Guo Wen-Ying, Liu Hui-Wei, Xu Feng
Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China.
World J Gastrointest Oncol. 2024 Dec 15;16(12):4685-4699. doi: 10.4251/wjgo.v16.i12.4685.
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.
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)γ pathway.
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)D] supplementation. 1,25(OH)D 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-PPARγ pathway were determined.
Supplementation with 1,25(OH)D relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD. Administration of 1,25(OH)D suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids, thereby directly relieving lipid accumulation and metabolism in hepatocytes. The VDR-PPARγ pathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)D.
Supplementation with 1,25(OH)D 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 VDR-PPARγ pathway. The involvement of 1,25(OH)D in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
非酒精性脂肪性肝病（NAFLD）是一种与代谢综合征相关的重要肝脏疾病，是全球肝脏疾病的主要原因，且在大多数国家其患病率呈上升趋势。维生素D对NAFLD的保护作用及其具体机制尚不清楚。
研究维生素D在NAFLD中的作用，以及维生素D如何通过维生素D受体（VDR）-过氧化物酶体增殖物激活受体（PPAR）γ途径影响NAFLD中肝巨噬细胞的极化。
给野生型C57BL/6小鼠喂食高脂饮食以建立NAFLD模型，并给予1,25-二羟基维生素D [1,25(OH)D]补充剂。将1,25(OH)D给予经脂质处理的RAW264.7巨噬细胞，并建立与AML12肝细胞的共培养体系。测定脂质积累、脂质代谢酶、M1/M2表型标志物、促炎细胞因子和VDR-PPARγ途径。
补充1,25(OH)D可减轻NAFLD中的肝脂肪变性，并降低肝巨噬细胞促炎M1极化。给予1,25(OH)D可抑制脂肪酸诱导的巨噬细胞促炎M1极化，从而直接减轻肝细胞中的脂质积累和代谢。VDR-PPARγ途径对逆转由1,25(OH)D给药调节的脂质诱导的巨噬细胞促炎M1极化有显著影响。
补充1,25(OH)D可改善NAFLD中的肝脂肪变性和脂质代谢，这与其逆转肝巨噬细胞促炎M1极化的能力有关，部分是通过调节VDR-PPARγ途径实现的。1,25(OH)D参与抑制脂肪酸诱导的巨噬细胞促炎M1极化，在减轻肝细胞脂质积累和代谢中起直接作用。
