摘要: Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor
(PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1a (HIF-1a), mimicked the hypoxiamediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, teantioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment
decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARc) and CCAAT/enhancer binding protein
(C/EBPa), but had no effect on HIF-1a, whereas hypoxia stabilized HIF-1a and decreased expression of C/EBPa, but not PPARc. Taken
together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via
distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes,and cardiovascular diseases.
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分类:
生物学
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生物医药
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引用:
ChinaXiv:201703.01019
(或此版本
ChinaXiv:201703.01019V1)
doi:10.12074/201703.01019
CSTR:32003.36.ChinaXiv.201703.01019.V1
- 推荐引用方式:
Chen, BY,Lam, KSL,Wang, Y,Wu, DH,Lam, MC,Shen, JG,Wong, LC,Hoo, RLC,Zhang, JL,Xu, AM.(2017).Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes.中国科学院科技论文预发布平台.[ChinaXiv:201703.01019]
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