Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner
| Autor: | Changtao Jiang, Pengcheng Wang, Huiying Liu, Song-Yang Zhang, Yang Zhao, Lulu Sun, Xun Wu, Xian Wang, Guangyi Zeng, Lei Wang, Bo Liu, Guoheng Xu, Yu Yan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hyperhomocysteinemia Lipolysis Clinical Biochemistry Nonalcoholic fatty liver White adipose tissue Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Internal medicine Adipocyte medicine Adipocytes Animals Hypoxia-inducible factor 1α Homocysteine lcsh:QH301-705.5 lcsh:R5-920 Triglyceride Organic Chemistry Fatty liver Hydrogen Peroxide medicine.disease Endoplasmic Reticulum Stress Mice Inbred C57BL Oxidative Stress 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry lcsh:Biology (General) Hepatocyte Adipocyte lipolysis ER oxidoreductin 1α Steatosis lcsh:Medicine (General) 030217 neurology & neurosurgery Research Paper |
| Zdroj: | Redox Biology, Vol 37, Iss, Pp 101742-(2020) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | 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. Graphical abstract Image 1 Highlights • 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. |
| Databáze: | OpenAIRE |
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