EFFECT OF VITAMIN D ON LIPID METABOLISM BY MODULATING MACROPHAGE POLARIZATION IN HEPATOCYTES

LUO Wen-jing; DONG Xian-wen; ZHAO Qiao-su; GUO Wen-ying; LIU Hui-wei; YE Hua

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (2) : 139-145.

ORIGINAL ARTICLES

LUO Wen-jing, DONG Xian-wen, ZHAO Qiao-su, GUO Wen-ying, LIU Hui-wei, YE Hua

Author information +

History +

Abstract

Objective To investigate the effect of vitamin D (VD) on lipid metabolism by modulating fatty-acid induced macrophage M1-M2 polarization in hepatocytes. Methods Saturated fatty acid treated RAW264.7 macrophages were cultured in DMEM with 1,25(OH)₂D3, and the conditioned medium (CM) were prepared. Then, AML12 hepatocytes were cultured in CM for 24 h. The M1/M2 polarization phenotype markers of macrophages were detected by RT- PCR. The mRNA and protein expressions of VDR and PPARγ of macrophages were detected by real-time PCR and Western blot, respectively. Lipid deposition in hepatocytes was examined by oil red O staining. The mRNA and protein expressions of lipometabolic enzymes of hepatocytes were detected by RT- PCR and Western blot, respectively. Results Compared to palmitic acid (PA) treated VD control group, the mRNA expressions of M1 phenotype markers, including iNOS2, TNFα and IL-6, and M2 phenotype marker IL-10, as well as the mRNA and protein expressions of VDR and PPARγ of macrophages in PA plus VD treated group were significantly decreased. Hepatocyte steatosis was obviously alleviated in the CM-PA plus VD treated group compared to the CM-PA plus VD control group. The mRNA and protein expressions of SREBP1C and FASN, as well as CPT1A of hepatocytes were significantly decreased in CM-PA plus VD treated group compared to the CM-PA plus VD control group. Conclusion VD supplementation improves lipid metabolism by reversing fatty-acid induced macrophage polarization through VDR/PPARγ pathway in hepatocytes.

Key words

vitamin D / macrophage / polarization / hepatocyte / lipid metabolism

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LUO Wen-jing, DONG Xian-wen, ZHAO Qiao-su, GUO Wen-ying, LIU Hui-wei, YE Hua. EFFECT OF VITAMIN D ON LIPID METABOLISM BY MODULATING MACROPHAGE POLARIZATION IN HEPATOCYTES[J]. Acta Nutrimenta Sinica. 2024, 46(2): 139-145

References

[1] Rinella ME.Nonalcoholic fatty liver disease: a systematic review[J]. JAMA, 2015, 313:2263–2273.
[2] Jablonski KL, Jovanovich A, Holmen J, et al. Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease[J]. Nutr Metab Cardiovasc Dis, 2013, 23:792–798.
[3] Barchetta I, Angelico F, Del Ben M, et al. Strong association between non-alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes[J]. BMC Med, 2011, 9:85.
[4] Zhu S, Wang Y, Luo F, et al. The level of vitamin D in children and adolescents with nonalcoholic fatty liver disease: a meta-analysis[J]. Biomed Res Int, 2019, 2019:7643542.
[5] Sakpal M, Satsangi S, Mehta M, et al. Vitamin D supplementation in patients with nonalcoholic fatty liver disease: a randomized controlled trial[J]. JGH Open, 2017, 1:62–67.
[6] Kitson MT, Pham A, Gordon A, et al. High-dose vitamin D supplementation and liver histology in NASH[J]. Gut, 2016, 65:717–718.
[7] Kazankov K, Jørgensen SMD, Thomsen KL, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16:145–159.
[8] Luo WJ, Xu QY, Wang Q, et al. Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease[J]. Sci Rep, 2017, 7:44612.
[9] Maina V, Sutti S, Locatelli I, et al. Bias in macrophage activation pattern influences non-alcoholic steatohe- patitis (NASH) in mice[J]. Clin Sci, 2012, 122:545–553.
[10] 罗雯静,董显文,赵巧素,等.维生素D调控Kupffer细胞极化在非酒精性脂肪性肝病防治中的作用[J].浙江医学,2023,45:916–921.
[11] Powell EE, Wong VW, Rinella M.Non-alcoholic fatty liver disease[J]. Lancet, 2021, 397:2212–2224.
[12] Charoenngam N, Holick MF.Immunologic effects of vitamin D on human health and disease[J]. Nutrients, 2020, 12:2097–2124.
[13] Dong B, Zhou Y, Wang W, et al. Vitamin D receptor activation in liver macrophages ameliorates hepatic inflammation, steatosis, and insulin resistance in mice[J]. Hepatology, 2020, 71:1559–1574.
[14] Locati M, Curtale G, Mantovani A.Diversity, mechanisms, and significance of macrophage plasticity[J]. Annu Rev Pathol, 2020, 15:123–147.
[15] Wang C, Ma C, Gong L, et al. Macrophage polarization and its role in liver disease[J]. Front Immunol, 2021, 12:803037.
[16] Bozic M, Guzmán C, Benet M, et al. Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis[J]. J Hepatol, 2016, 65:748–757.
[17] Di Rosa M, Malaguarnera G, De Gregorio C, et al. Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages[J]. Cell Immunol, 2012, 280:36–43.
[18] Daniel B, Nagy G, Czimmerer Z, et al. The nuclear receptor PPARγ controls progressive macrophage polarization as a ligand-insensitive epigenomic ratchet of transcriptional memory[J]. Immunity, 2018, 49:615–626.
[19] Alimirah F, Peng X, Yuan L, et al. Crosstalk between the peroxisome proliferator-activated receptor γ(PPARγ) and the vitamin D receptor (VDR) in human breast cancer cells: PPARγ binds to VDR and inhibits 1α,25- dihydroxyvitamin D3 mediated transactivation[J]. Exp Cell Res, 2012, 318:2490–2497.
[20] Ramos LF, Silva CM, Pansa CC, et al. Non-alcoholic fatty liver disease: molecular and cellular interplays of the lipid metabolism in a steatotic liver[J]. Expert Rev Gastroenterol Hepatol, 2021, 15:25–40.
[21] Smith GI, Shankaran M, Yoshino M, et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease[J]. J Clin Invest, 2020, 130:1453–1460.
[22] Alves-Bezerra M, Cohen DE.Triglyceride metabolism in the liver[J]. Compr Physiol, 2017, 8:1–8.
[23] Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018, 24:908–922.