Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.
Gerald Bronfman Department of Oncology, Faculty of Medicine, McGill University, Montreal, QC H4A 3T2, Canada.
Cells. 2019 Mar 3;8(3):214. doi: 10.3390/cells8030214.
Oxygen deprivation or hypoxia characterizes a number of serious pathological conditions and elicits a number of adaptive changes that are mainly mediated at the transcriptional level by the family of hypoxia-inducible factors (HIFs). The HIF target gene repertoire includes genes responsible for the regulation of metabolism, oxygen delivery and cell survival. Although the involvement of HIFs in the regulation of carbohydrate metabolism and the switch to anaerobic glycolysis under hypoxia is well established, their role in the control of lipid anabolism and catabolism remains still relatively obscure. Recent evidence indicates that many aspects of lipid metabolism are modified during hypoxia or in tumor cells in a HIF-dependent manner, contributing significantly to the pathogenesis and/or progression of cancer and metabolic disorders. However, direct transcriptional regulation by HIFs has been only demonstrated in relatively few cases, leaving open the exact and isoform-specific mechanisms that underlie HIF-dependency. This review summarizes the evidence for both direct and indirect roles of HIFs in the regulation of genes involved in lipid metabolism as well as the involvement of HIFs in various diseases as demonstrated by studies with transgenic animal models.
缺氧或低氧是许多严重病理状况的特征，并引发了许多适应性变化，这些变化主要在转录水平上由缺氧诱导因子 (HIF) 家族介导。HIF 的靶基因谱包括负责调节代谢、氧输送和细胞存活的基因。尽管 HIFs 在调节碳水化合物代谢和缺氧下的无氧糖酵解中的作用已得到充分证实，但它们在控制脂肪合成和分解代谢中的作用仍然相对模糊。最近的证据表明，在缺氧或肿瘤细胞中，许多脂代谢方面会发生变化，这对癌症和代谢紊乱的发病机制和/或进展有重要贡献。然而，只有在相对较少的情况下证明了 HIF 的直接转录调节，这使得 HIF 依赖性的具体和同工型特异性机制仍然存在争议。这篇综述总结了 HIF 直接和间接调节脂代谢相关基因的证据，以及 HIF 在各种疾病中的作用，这些作用已通过转基因动物模型的研究得到证明。
