Luo WJ, Dong XW, Ye H, Zhao QS, Zhang QB, Guo WY, Liu HW, Xu F. Vitamin D 1,25-Dihydroxyvitamin D3 reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization. World J Gastrointest Oncol 2024; 16(12): 4685-4699 [PMID: 39678811 DOI: 10.4251/wjgo.v16.i12.4685]
Corresponding Author of This Article
Feng Xu, MAMS, Chief Physician, Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, No. 57 Xingning Road, Ningbo 315000, Zhejiang Province, China. xufeng200468@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Wen-Jing Luo, Xian-Wen Dong, Hua Ye, Qiao-Su Zhao, Qiu-Bo Zhang, Wen-Ying Guo, Hui-Wei Liu, Feng Xu, Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, China
Author contributions: Luo WJ, Dong XW and Ye H designed the research study; Zhao QS, Zhang QB and Guo WY performed the research; Liu HW and Xu F conducted experiments, analyzed the data; All authors contributed to editorial changes in the manuscript; All authors read and approved the final manuscript.
Supported bythe Natural Science Foundation of Ningbo, No. 202003N4234; and Medical and Health Research Project of Zhejiang Province, No. 2024KY1477.
Institutional animal care and use committee statement: This study was approved by the Ningbo University Animal Care and Use Committee according to the criteria set by Ningbo Medical Center Lihuili Hospital, No. IACUC202013.
Conflict-of-interest statement: The authors declare that they have no competing interests
Data sharing statement: The datasets used and analysed during the current study are available from the corresponding author on reasonable request at xufeng200468@126.com.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Xu, MAMS, Chief Physician, Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, No. 57 Xingning Road, Ningbo 315000, Zhejiang Province, China. xufeng200468@126.com
Received: April 16, 2024 Revised: September 9, 2024 Accepted: October 8, 2024 Published online: December 15, 2024 Processing time: 210 Days and 3 Hours
Abstract
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)γ pathway.
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)2D3] supplementation. 1,25(OH)2D3 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.
RESULTS
Supplementation with 1,25(OH)2D3 relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD. Administration of 1,25(OH)2D3 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)2D3.
CONCLUSION
Supplementation with 1,25(OH)2D3 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)2D3 in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
Core Tip: Supplementation with 1,25-dihydroxy-vitamin D [1,25(OH)2D3] improved hepatic steatosis and lipid metabolism in nonalcoholic fatty liver disease, linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages, partially by regulating the vitamin D receptor-peroxisome proliferator activated receptor γ pathway. The involvement of 1,25(OH)2D3 in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
