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.
复制标题
同型半胱氨酸通过以 HIF1α-ERO1α 依赖的氧化应激方式激活脂肪细胞脂肪分解来促进肝脂肪变性。
DOI：
10.1016/j.redox.2020.101742
复制
发表时间：
2020-10
期刊：
影响因子：
11.4
通讯作者：
Jiang C
中科院分区：
文献类型：
--
作者：
Yan Y;Wu X;Wang P;Zhang S;Sun L;Zhao Y;Zeng G;Liu B;Xu G;Liu H;Wang L;Wang X;Jiang C
高同型半胱氨酸血症（HHcy）与肝脏疾病有关，如非酒精性脂肪肝（NAFL）。虽然NAFL的确切发病机制在很大程度上仍然是未知的，但器官之间的联系似乎起着至关重要的作用。本研究旨在探讨白色脂肪组织在同型半胱氨酸（Hcy）诱导的NAFL中的作用。收集非高同型半胱氨酸血症或高同型半胱氨酸血症个体的血液样本，以评估Hcy与甘油三酯（TG）或游离脂肪酸（FFA）水平之间的相关性。C57 BL/6小鼠维持高蛋氨酸饮食或在饮用水中施用Hcy（1.8g/L）以建立HHcy小鼠模型。我们证明，同型半胱氨酸激活脂肪细胞脂解，这种变化是伴随着增加释放的脂肪酸和甘油。过量的游离脂肪酸被肝细胞摄取，导致脂质在肝脏中蓄积。阿昔莫司（0.08 g kg −1 day −1）（一种有效的脂解化学抑制剂）治疗可显著降低Hcy诱导的NAFL。缺氧诱导因子1α（HIF 1 α）-内质网氧化还原蛋白1α（ERO 1 α）介导的途径促进H2 O2积累，诱导内质网（ER）过氧化、ER应激和ER-脂滴间更紧密的相互作用，从而激活脂解反应。总之，这项研究表明，同型半胱氨酸激活脂肪细胞脂解，并提出了潜在的效用，有针对性的ER氧化还原稳态治疗同型半胱氨酸诱导的NAFL。同型半胱氨酸促进脂肪细胞脂解过程。通过阿昔莫司抑制脂肪细胞脂解可改善Hcy诱导的非酒精性脂肪肝脂肪细胞脂解反应依赖于ERO 1 α介导的氧化应激。脂肪细胞HIF 1 α的活化介导ERO 1 α的上调。脂肪细胞HIF 1 α缺乏可导致Hcy诱导的脂解反应和非酒精性脂肪肝
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. Hcy elevates adipocyte lipolysis process. Inhibition of adipocyte lipolysis via acipimox improves the Hcy-induced nonalcoholic fatty liver. Adipocyte lipolytic response relies on ERO1α-mediated oxidative stress. Activation of adipocyte HIF1α mediates ERO1α upregulation. Deficiency of adipocyte HIF1α alleviates the Hcy-induced lipolytic response and nonalcoholic fatty liver.
登录
查看更多内容
影响因子：
5.4
作者：
Ganguly P;Alam SF
通讯作者：
Alam SF
影响因子：
5.3
作者：
Bogdanovic E;Kraus N;Patsouris D;Diao L;Wang V;Abdullahi A;Jeschke MG
通讯作者：
Jeschke MG
影响因子：
4.8
作者：
Hansen, Henning Gram;Schmidt, Jonas Damgard;Ellgaard, Lars
通讯作者：
Ellgaard, Lars
影响因子：
4
作者：
Eletto, Davide;Chevet, Eric;Appenzeller-Herzog, Christian
通讯作者：
Appenzeller-Herzog, Christian
影响因子：
25.7
作者：
Fan, JG;Zhu, J;Chen, SY
通讯作者：
Chen, SY