AMELIORATIVE EFFECT OF VITAMIN D ON OLEIC ACID-INDUCED LIPID ACCUMULATION IN HEPATOCYTES THROUGH THE FXR PATHWAY

JI Shu-qi; HAN Yan-yang; DONG Ya-jing; YU Yuan-tong; HAN Hao

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Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (5) : 470-476.

ORIGINAL ARTICLES

AMELIORATIVE EFFECT OF VITAMIN D ON OLEIC ACID-INDUCED LIPID ACCUMULATION IN HEPATOCYTES THROUGH THE FXR PATHWAY

JI Shu-qi, HAN Yan-yang, DONG Ya-jing, YU Yuan-tong, HAN Hao

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Abstract

Objective To explore the effect of vitamin D on oleic acid (OA)-induced lipid accumulation in hepatocytes through the farnesoid X receptor (FXR) pathway. Methods HepG2 cells were divided into three groups. The control group was not treated. The OA group was treated with OA (0.5mmol/L) to induce lipid accumulation in HepG2 cells, and the OA+VD group was treated with OA (0.5mmol/L) and 1,25(OH)₂D₃(0.05mmol/L). The lipid accumulation in the cells was observed by Oil Red O staining. FXR expression in the nucleus was observed with the merged images, in which the expression of FXR in the cells was detected with immunofluorescence staining and that in the cell nuclei were labeled with DAPI. The protein expressions of FXR, SREBP-1c, SCD-1, FAS, PPARα, and CPT-1A were assayed by Western blot. Results Compared with the control group, OA treatment resulted in significant intracellular lipid droplet accumulation, and was significantly ameliorated by the simultaneous treatment of 1,25(OH)₂D₃. The results of mechanistic investigations revealed that 1,25(OH)₂D₃ treatment significantly enhanced the protein expression of FXR in the nuclei compared to the OA treatment. Meanwhile, 1,25(OH)₂D₃ treatment also significantly down-regulated the expression of key proteins involved in fatty acid synthesis (SREBP-1c, SCD-1, and FAS) and up-regulated the expression of key proteins involved in β-oxidation of fatty acid (PPARα and CPT-1A). Conclusion 1,25(OH)2D3 has the potential to ameliorate OA-induced lipid accumulation in HepG2 cells via the FXR pathway.

Key words

vitamin D₃ / HepG2 cells / oleic acid / lipid accumulation / FXR

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JI Shu-qi, HAN Yan-yang, DONG Ya-jing, YU Yuan-tong, HAN Hao. AMELIORATIVE EFFECT OF VITAMIN D ON OLEIC ACID-INDUCED LIPID ACCUMULATION IN HEPATOCYTES THROUGH THE FXR PATHWAY[J]. Acta Nutrimenta Sinica. 2025, 47(5): 470-476

References

[1] 中华医学会肝病学分会.代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J].实用肝脏病杂志,2024,27:494–510.
[2] Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease[J]. Hepatology, 2023,77:1797-1835.
[3] Teng ML, Ng CH, Huang DQ, et al. Global incidence and prevlence of nonalcoholic fatty liver disease[J]. Clin Mol Hepatol, 2023,29(Suppl):S32–S42.
[4] Le MH, Yeo YH, Zou B, et al. Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical Bayesian approach[J]. Clin Mol Hepatol, 2022,28:841–850.
[5] Zhou J, Zhou F, Wang W, et al. Epidemiological Features of MAFLD From 1999 to 2018 in China[J]. Hepatology, 2020,71:1851–1864.
[6] Yuan S, Larsson SC. Inverse association between serum 25-Hydroxyvitamin D and nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol, 2023,21:398–405.e4.
[7] Mohamed AA, Halim AA, Mohamed S, et al. The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients: a randomized placebo controlled trial[J]. Front Pharmacol, 2023,14:1149967.
[8] Zhang XL, Chen L, Yang J, et al. Vitamin D alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism[J]. Front Microbiol, 2023,14:1117644.
[9] Xiang J, Zhang Z, Xie H, et al. Effect of different bile acids on the intestine through enterohepatic circulation based on FXR[J]. Gut Microbes, 2021,13:1949095.
[10] Chiang JYL, Ferrell JM.Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy[J]. Am J Physiol Gastrointest Liver Physiol, 2020,318:G554–G573.
[11] Yang Z, Danzeng A, Liu Q, et al. The role of nuclear receptors in the pathogenesis and treatment of non-alcoholic fatty liver disease[J]. Int J Biol Sci, 2024,20:113–126.
[12] Zhou S, You H, Qiu S, et al. A new perspective on MAFLD: Focusing on the crosstalk between peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR)[J]. Biomed Pharmacother, 2022,54:113577.
[13] Alshawsh MA, Alsalahi A, Alshehade SA, et al. A comparison of the gene expression profiles of non-alcoholic fatty liver disease between animal models of a high-fat diet and methionine-choline-deficient diet[J]. Molecules, 2022,27:858.
[14] Zhang M, Bai X, Du Q, et al. the different mechanisms of lipid accumulation in hepatocytes induced by oleic acid/palmitic acid and high-fat diet[J]. Molecules, 2023,28:6714.
[15] Chen Q, Zhao L, Mei L, et al. Vitamin C and vitamin D₃ alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism via the gut-liver axis[J]. Front Pharmacol, 2023,14:1163694.
[16] Lee SB, Jin MH, Yoon JH.The contribution of vitamin D insufficiency to the onset of steatotic liver disease among individuals with metabolic dysfunction[J]. Sci Rep, 2024,14:6714.
[17] Chang E.Vitamin D Mitigates hepatic fat accumulation and inflammation and increases SIRT1/AMPK expression in AML-12 hepatocytes[J]. Molecules, 2024,29:1401.
[18] Stofan M, Guo GL.Bile acids and FXR: novel targets for liver diseases[J]. Front Med, 2020,7:544.
[19] Song Z, Xiaoli AM, Yang F.Regulation and metabolic significance of de novo lipogenesis in adipose tissues[J]. Nutrients, 2018,10:1383.
[20] Hu P, Li K, Peng X, et al. Nuclear receptor PPARα as a therapeutic target in diseases associated with lipid metabolism disorders[J]. Nutrients, 2023,15:4772.
[21] Donde H, Ghare S, Joshi-Barve S, et al. Tributyrin inhibits ethanol-induced epigenetic repression of CPT-1A and attenuates hepatic steatosis and injury[J]. Cell Mol Gastroenterol Hepatol, 2020,9:569–585.
[22] Tahri-Joutey M, Andreoletti P, Surapureddi S, et al. Mechanisms mediating the regulation of peroxisomal fatty acid beta-oxidation by PPARα[J]. Int J Mol Sci, 2021,22:8969.
[23] Cominguez DC, Park YJ, Kang YM, et al. Clitorin ameliorates western diet-induced hepatic steatosis by regulating lipogenesis and fatty acid oxidation in vivo and in vitro[J]. Sci Rep, 2022,12:4154.
[24] He J, Yang Y, Zhang F, et al. Effects of Poria cocos extract on metabolic dysfunction-associated fatty liver disease via the FXR/PPARα-SREBPs pathway[J]. Front Pharmacol, 2022,13:1007274.
[25] Meng Q, Duan XP, Wang CY, et al. Alisol B 23-acetate protects against non-alcoholic steatohepatitis in mice via farnesoid X receptor activation[J]. Acta Pharmacol Sin, 2017,38:69–79.
[26] Ke Z, Fan C, Li J, et al. Nobiletin intake attenuates hepatic lipid profiling and oxidative stress in hfd-induced nonalcoholic-fatty-liver-disease mice[J]. Molecules, 2023,28:2570.
[27] Du T, Xiang L, Zhang J, et al. Vitamin D improves hepatic steatosis in MAFLD via regulation of fatty acid uptake and β-oxidation[J]. Front Endocrinol, 2023,14:1138078.