Gaspar Joana M, Velloso Lício A
Post-Graduation in Biochemistry, Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Brazil.
Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Front Neurosci. 2018 Nov 1;12:813. doi: 10.3389/fnins.2018.00813. eCollection 2018.
The hypothalamus plays a major role in the regulation of food intake and energy expenditure. In the last decade, it was demonstrated that consumption of high-fat diets triggers the activation of an inflammatory process in the hypothalamus, inducing neurofunctional alterations and contributing to the development of obesity. Hypoxia-inducible factors (HIFs) are key molecules that regulate cellular responses to inflammation and hypoxia, being essential for the normal cell function and survival. Currently, evidence points to a role of HIF pathway in metabolic regulation that could also be involved in the progression of obesity and metabolic diseases. The challenge is to understand how HIF modulation impacts body mass gain and metabolic disorders such as insulin resistance. Distinct animal models with tissue-specific knocking-out or overexpression of hypoxia signaling pathway genes revealed a cell-specificity in the activation of HIF pathways, and some of them have opposite phenotypes among the various HIFs gain- and loss-of-function mouse models. In this review, we discuss the major findings that provide support for a role of HIF pathway involvement in the regulation of metabolism, especially in glucose and energy homeostasis.
下丘脑在食物摄入和能量消耗的调节中起主要作用。在过去十年中，研究表明，食用高脂饮食会引发下丘脑炎症过程的激活，导致神经功能改变，并促使肥胖的发展。缺氧诱导因子（HIFs）是调节细胞对炎症和缺氧反应的关键分子，对正常细胞功能和存活至关重要。目前，有证据表明HIF通路在代谢调节中发挥作用，这也可能与肥胖和代谢性疾病的进展有关。挑战在于了解HIF调节如何影响体重增加和代谢紊乱，如胰岛素抵抗。通过组织特异性敲除或过表达缺氧信号通路基因的不同动物模型揭示了HIF通路激活中的细胞特异性，并且在各种HIF功能获得和功能丧失小鼠模型中，其中一些具有相反的表型。在这篇综述中，我们讨论了主要研究结果，这些结果支持HIF通路参与代谢调节，特别是在葡萄糖和能量稳态方面的作用。
