Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Department of Physiology, University of Murcia, Murcia, Spain.
Endocr Rev. 2018 Jun 1;39(3):261-273. doi: 10.1210/er.2017-00193.
Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension, and has become a serious public health problem. Mammals have developed a circadian clock located in the hypothalamic suprachiasmatic nuclei (SCN) that responds to the environmental light-dark cycle. Clocks similar to the one located in the SCN are found in peripheral tissues, such as the kidney, liver, and adipose tissue. The circadian clock regulates metabolism and energy homeostasis in peripheral tissues by mediating activity and/or expression of key metabolic enzymes and transport systems. Knockouts or mutations in clock genes that lead to disruption of cellular rhythmicity have provided evidence to the tight link between the circadian clock and metabolism. In addition, key proteins play a dual role in regulating the core clock mechanism, as well as adipose tissue metabolism, and link circadian rhythms with lipogenesis and lipolysis. Adipose tissues are distinguished as white, brown, and beige (or brite), each with unique metabolic characteristics. Recently, the role of the circadian clock in regulating the differentiation into the different adipose tissues has been investigated. In this review, the role of clock proteins and the downstream signaling pathways in white, brown, and brite adipose tissue function and differentiation will be reviewed. In addition, chronodisruption and metabolic disorders and clinical aspects of circadian adiposity will be addressed.
肥胖是胰岛素抵抗和高血压等疾病发展的一个主要危险因素,已成为严重的公共卫生问题。哺乳动物在位于下丘脑视交叉上核(SCN)的部位进化出了生物钟,以响应环境的光-暗循环。类似于位于 SCN 中的生物钟也存在于肾脏、肝脏和脂肪组织等外周组织中。生物钟通过调节关键代谢酶和转运系统的活性和/或表达来调节外周组织的代谢和能量稳态。时钟基因的敲除或突变导致细胞节律性紊乱,为生物钟与代谢之间的紧密联系提供了证据。此外,关键蛋白在调节核心时钟机制以及脂肪组织代谢方面发挥双重作用,并将昼夜节律与脂肪生成和脂肪分解联系起来。脂肪组织分为白色、棕色和米色(或 beige),每种组织都具有独特的代谢特征。最近,人们研究了生物钟在调节不同脂肪组织分化中的作用。在这篇综述中,将讨论时钟蛋白及其下游信号通路在白色、棕色和米色脂肪组织功能和分化中的作用。此外,还将讨论生物钟紊乱与代谢紊乱以及昼夜节律性肥胖的临床方面。