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  • Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner.

Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner.

Redox biology (2020-10-13)
Yu Yan, Xun Wu, Pengcheng Wang, Songyang Zhang, Lulu Sun, Yang Zhao, GuangYi Zeng, Bo Liu, Guoheng Xu, Huiying Liu, Lei Wang, Xian Wang, Changtao Jiang
摘要

Hyperhomocysteinemia (HHcy) is related to liver diseases, such as nonalcoholic fatty liver (NAFL). Although the precise pathogenesis of NAFL is still largely unknown, the links between organs seem to play a vital role. The current study aimed to explore the role of white adipose tissue in homocysteine (Hcy)-induced NAFL. Blood samples from nonhyperhomocysteinemia or hyperhomocysteinemia individuals were collected to assess correlation between Hcy and triglyceride (TG) or free fatty acids (FFAs) levels. C57BL/6 mice were maintained on a high-methionine diet or administered with Hcy (1.8 g/L) in the drinking water to establish an HHcy mouse model. We demonstrated that Hcy activated adipocyte lipolysis and that this change was accompanied by an increased release of FFAs and glycerol. Excessive FFAs were taken up by hepatocyte, which resulted in lipid accumulation in the liver. Treatment with acipimox (0.08 g kg -1 day -1), a potent chemical inhibitor of lipolysis, markedly decreased Hcy-induced NAFL. Mechanistically, hypoxia-inducible factor 1α (HIF1α)-endoplasmic reticulum oxidoreductin 1α (ERO1α) mediated pathway promoted H2O2 accumulation and induced endoplasmic reticulum (ER) overoxidation, ER stress and more closed ER-lipid droplet interactions, which were responsible for activating the lipolytic response. In conclusion, this study reveals that Hcy activates adipocyte lipolysis and suggests the potential utility of targeted ER redox homeostasis for treating Hcy-induced NAFL.

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抗-β-肌动蛋白−过氧化物酶抗体,小鼠单克隆 小鼠抗, clone AC-15, purified from hybridoma cell culture
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抗小鼠IgG(全分子)-过氧化物酶 山羊抗, affinity isolated antibody, buffered aqueous solution
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抗-α微管蛋白抗体,小鼠单克隆抗体, clone B-5-1-2, purified from hybridoma cell culture
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阿西莫司, ≥99% (TLC)
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1 g
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抗-Ero1 5抗体(克隆2G4/12), clone 2G4/12, from mouse
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货号包装规格是否有货价格数量
1 g
预计发货时间 2025年5月22日
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¥1,994.09
25 g
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¥15,612.08
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¥123,583.33