首页|维生素D调控巨噬细胞极化对肝细胞脂质代谢的作用及机制

维生素D调控巨噬细胞极化对肝细胞脂质代谢的作用及机制

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目的 探讨维生素D(vitamin D,VD)调控脂肪酸诱导的巨噬细胞M1-M2 极化表型转变对肝细胞脂质代谢的直接作用及机制.方法 体外饱和脂肪酸孵育培养小鼠巨噬细胞RAW264.7并予活性VD-1,25(OH)2D3补充干预,制备相应的条件培养液体外培养小鼠肝细胞AML12.Real-time PCR检测巨噬细胞M1/M2 极化基因表达水平,Real-time PCR、Western blot 分别检测巨噬细胞 VD 受体(VD receptor,VDR)/过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)基因、蛋白表达水平;油红O染色观察肝细胞内脂质沉积表现,Real-time PCR、Western blot分别检测肝细胞脂质合成和分解代谢相关酶类基因、蛋白表达水平.结果 体外饱和脂肪酸作用下,与VD对照组相较,VD补充组巨噬细胞M1 极化基因诱生型一氧化氮合酶 2(inducible nitric oxide synthase 2,iNOS2)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)及M2 极化基因白细胞介素-10(interleukin-10,IL-10)mRNA表达水平均明显降低,巨噬细胞VDR/PPARγ mRNA和蛋白表达水平均明显降低.体外饱和脂肪酸作用的巨噬细胞条件培养液孵育肝细胞,与 VD 对照组相较,VD 补充组肝细胞脂肪变性明显减少,肝细胞脂质合成代谢酶[固醇调节元件结合蛋白 1C(sterol-regulatory element binding protein 1C,SREBP1C)、脂肪酸合酶(fatty acid synthase,FASN)]mRNA 和蛋白表达水平均明显降低,脂质分解代谢酶肉碱棕榈酰转移酶 1A(carnitine palmitoyltransferase 1A,CPT1A)mRNA和蛋白表达水平明显降低.结论 补充VD介导VDR/PPARγ 通路逆转脂肪酸诱导的巨噬细胞极化表型直接影响肝细胞脂质代谢水平并改善肝细胞脂肪变性.[营养学报,2024,46(2):139-145]
EFFECT OF VITAMIN D ON LIPID METABOLISM BY MODULATING MACROPHAGE POLARIZATION IN HEPATOCYTES
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.[ACTA NUTRIMENTA SINICA,2024,46(2):139-145]

vitamin Dmacrophagepolarizationhepatocytelipid metabolism

罗雯静、董显文、赵巧素、郭雯莹、柳惠未、叶桦

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宁波大学附属李惠利医院消化内科,宁波 315000

维生素D 巨噬细胞 极化 肝细胞 脂质代谢

宁波市自然科学基金浙江省医药卫生科技计划

202003N42342024KY1477

2024

营养学报
中国营养学会 军事医学科学院卫生学环境医学研究所

营养学报

CSTPCD北大核心
影响因子:0.654
ISSN:0512-7955
年,卷(期):2024.46(2)
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