Institute of Biochemistry, Food Science, and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Endocr Rev. 2010 Feb;31(1):1-24. doi: 10.1210/er.2009-0014. Epub 2009 Oct 23.
Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Human homeostatic systems have adapted to daily changes in light and dark in a way that the body anticipates the sleep and activity periods. Mammals have developed an endogenous circadian clock located in the suprachiasmatic nuclei of the anterior hypothalamus that responds to the environmental light-dark cycle. Similar clocks have been found in peripheral tissues, such as the liver, intestine, and adipose tissue, regulating cellular and physiological functions. The circadian clock has been reported to regulate metabolism and energy homeostasis in the liver and other peripheral tissues. This is achieved by mediating the expression and/or activity of certain metabolic enzymes and transport systems. In return, key metabolic enzymes and transcription activators interact with and affect the core clock mechanism. In addition, the core clock mechanism has been shown to be linked with lipogenic and adipogenic pathways. Animals with mutations in clock genes that disrupt cellular rhythmicity have provided evidence for the relationship between the circadian clock and metabolic homeostasis. In addition, clinical studies in shift workers and obese patients accentuate the link between the circadian clock and metabolism. This review will focus on the interconnection between the circadian clock and metabolism, with implications for obesity and how the circadian clock is influenced by hormones, nutrients, and timed meals.
肥胖已成为严重的公共卫生问题，也是导致胰岛素抵抗和高血压等疾病的主要危险因素之一。人体的内稳态系统已经适应了日常的光暗变化，身体会预测睡眠和活动期。哺乳动物在其前下丘脑的视交叉上核中发展出了内在的生物钟，以响应环境的光暗周期。在肝脏、肠道和脂肪组织等外周组织中也发现了类似的时钟，调节细胞和生理功能。据报道，生物钟调节肝脏和其他外周组织中的代谢和能量稳态。这是通过调节某些代谢酶和转运系统的表达和/或活性来实现的。反过来，关键的代谢酶和转录激活因子相互作用并影响核心时钟机制。此外，核心时钟机制已被证明与脂肪生成和脂肪形成途径有关。时钟基因发生突变导致细胞节律性紊乱的动物为生物钟和代谢稳态之间的关系提供了证据。此外，轮班工作者和肥胖患者的临床研究强调了生物钟与代谢之间的联系。这篇综述将重点关注生物钟和代谢之间的相互联系，及其对肥胖的影响，以及生物钟如何受到激素、营养物质和定时进餐的影响。
