Ban Jae-Jun, Ruthenborg Robin J, Cho Kevin W, Kim Jung-Whan
Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA.
Hypoxia (Auckl). 2014 Nov 13;2:171-183. doi: 10.2147/HP.S68771. eCollection 2014.
In obesity, dysregulated metabolism and aberrant expansion of adipose tissue lead to the development of tissue hypoxia that plays an important role in contributing to obesity-associated metabolic disorders. Recent studies utilizing adipocyte-specific hypoxia-inducible factor-α (HIF-α) gain- or loss-of-function animal models highlight the pivotal involvement of hypoxic responses in the pathogenesis of obesity-associated inflammation and insulin resistance. HIF-1α, a master transcription factor of oxygen homeostasis, induces inflammation and insulin resistance in obesity, whereas its isoform, HIF-2α, exerts opposing functions in these obesity-associated metabolic phenotypes. In this review, recent evidence elucidating functional implications of adipocyte HIFs in obesity and, more importantly, how these regulate obesity-associated inflammation, fibrosis, and insulin resistance will be discussed. Further, we propose that modulation of HIF-1 could be a potential novel therapeutic strategy for antidiabetic treatment.
在肥胖症中，代谢失调和脂肪组织异常扩张会导致组织缺氧，这在肥胖相关代谢紊乱的发生发展中起重要作用。最近利用脂肪细胞特异性缺氧诱导因子-α（HIF-α）功能获得或功能缺失动物模型进行的研究强调了缺氧反应在肥胖相关炎症和胰岛素抵抗发病机制中的关键作用。HIF-1α是氧稳态的主要转录因子，在肥胖症中诱导炎症和胰岛素抵抗，而其异构体HIF-2α在这些肥胖相关代谢表型中发挥相反作用。在本综述中，将讨论阐明脂肪细胞HIFs在肥胖症中的功能意义的最新证据，更重要的是，这些证据如何调节肥胖相关炎症、纤维化和胰岛素抵抗。此外，我们提出调节HIF-1可能是抗糖尿病治疗的一种潜在新策略。
