{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:23:44Z","timestamp":1792794224934,"version":"4.5.0"},"reference-count":49,"publisher":"Baishideng Publishing Group Inc.","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastrointest Oncol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n          <jats:p>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.<\/jats:p>\n          <jats:p>AIM<\/jats:p>\n          <jats:p>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)\u03b3 pathway.<\/jats:p>\n          <jats:p>METHODS<\/jats:p>\n          <jats:p>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-PPAR\u03b3 pathway were determined.<\/jats:p>\n          <jats:p>RESULTS<\/jats:p>\n          <jats:p>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-PPAR\u03b3 pathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)2D3.<\/jats:p>\n          <jats:p>CONCLUSION<\/jats:p>\n          <jats:p>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-PPAR\u03b3 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.<\/jats:p>","DOI":"10.4251\/wjgo.v16.i12.4685","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T06:17:27Z","timestamp":1731046647000},"page":"4685-4699","source":"Crossref","is-referenced-by-count":15,"title":["Vitamin D 1,25-Dihydroxyvitamin D<sub>3<\/sub> reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization"],"prefix":"10.4251","volume":"16","author":[{"given":"Wen-Jing","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Wen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao-Su","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ying","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2024,12,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.5370"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0806-8"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32511-3"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2947-0"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.12.012"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072097"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186644"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/nu12113302"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.011487"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i19.3407"},{"key":"B11","unstructured":"Wang X, Li W, Zhang Y, Yang Y, Qin G. 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