Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Endocrinol (Lausanne). 2020 Feb 27;11:95. doi: 10.3389/fendo.2020.00095. eCollection 2020.
Over the past decade, the increasing prevalence of obesity and its associated metabolic disorders constitutes one of the most concerning healthcare issues for countries worldwide. In an effort to curb the increased mortality and morbidity derived from the obesity epidemic, various therapeutic strategies have been developed by researchers. In the recent years, advances in the field of adipocyte biology have revealed that the thermogenic adipose tissue holds great potential in ameliorating metabolic disorders. Additionally, epigenetic research has shed light on the effects of histone acetylation on adipogenesis and thermogenesis, thereby establishing the essential roles which histone acetyltransferases (HATs) and histone deacetylases (HDACs) play in metabolism and systemic energy homeostasis. In regard to the therapeutic potential of thermogenic adipocytes for the treatment of metabolic diseases, herein, we describe the current state of knowledge of the regulation of thermogenic adipocyte differentiation and adaptive thermogenesis through histone acetylation. Furthermore, we highlight how different HATs and HDACs maintain the epigenetic transcriptional network to mediate the pathogenesis of various metabolic comorbidities. Finally, we provide insights into recent advances of the potential therapeutic applications and development of HAT and HDAC inhibitors to alleviate these pathological conditions.
在过去的十年中,肥胖及其相关代谢紊乱的发病率不断上升,成为全球各国最关注的医疗保健问题之一。为了遏制肥胖流行带来的死亡率和发病率的上升,研究人员已经开发出各种治疗策略。近年来,脂肪细胞生物学领域的进展表明,产热脂肪组织在改善代谢紊乱方面具有巨大潜力。此外,表观遗传学研究揭示了组蛋白乙酰化对脂肪生成和产热的影响,从而确立了组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)在代谢和全身能量平衡中的重要作用。关于产热脂肪细胞治疗代谢疾病的治疗潜力,本文描述了通过组蛋白乙酰化调节产热脂肪细胞分化和适应性产热的最新知识状态。此外,我们强调了不同的 HAT 和 HDAC 如何维持表观遗传转录网络,从而介导各种代谢合并症的发病机制。最后,我们深入探讨了 HAT 和 HDAC 抑制剂的潜在治疗应用和开发的最新进展,以减轻这些病理状况。