Institute for Diabetes, Obesity, and Metabolism, Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nutrients. 2022 Jul 29;14(15):3136. doi: 10.3390/nu14153136.
Obesity and other metabolic diseases are major public health issues that are particularly prevalent in industrialized societies where circadian rhythmicity is disturbed by shift work, jet lag, and/or social obligations. In mammals, daylight entrains the hypothalamic suprachiasmatic nucleus (SCN) to a ≈24 h cycle by initiating a transcription/translation feedback loop (TTFL) of molecular clock genes. The downstream impacts of the TTFL on clock-controlled genes allow the SCN to set the rhythm for the majority of physiological, metabolic, and behavioral processes. The TTFL, however, is ubiquitous and oscillates in tissues throughout the body. Tissues outside of the SCN are entrained to other signals, such as fed/fasting state, rather than light input. This system requires a considerable amount of biological flexibility as it functions to maintain homeostasis across varying conditions contained within a 24 h day. In the face of either circadian disruption (e.g., jet lag and shift work) or an obesity-induced decrease in metabolic flexibility, this finely tuned mechanism breaks down. Indeed, both human and rodent studies have found that obesity and metabolic disease develop when endogenous circadian pacing is at odds with the external cues. In the following review, we will delve into what is known on the circadian rhythmicity of nutrient metabolism and discuss obesity as a circadian disease.
肥胖症和其他代谢性疾病是重大的公共卫生问题，在工业化社会中尤为普遍，这些社会中的轮班工作、时差和/或社会义务扰乱了昼夜节律。在哺乳动物中，日光通过启动分子钟基因的转录/翻译反馈环（TTFL）使下丘脑视交叉上核（SCN）同步到约 24 小时的周期。TTFL 对时钟控制基因的下游影响使 SCN 能够为大多数生理、代谢和行为过程设定节奏。然而，TTFL 无处不在，并在全身组织中振荡。SCN 以外的组织被其他信号（例如进食/禁食状态）而不是光输入所同步。这个系统需要相当大的生物灵活性，因为它的功能是在 24 小时的一天内维持不同条件下的体内平衡。在昼夜节律紊乱（例如时差和轮班工作）或肥胖引起的代谢灵活性下降的情况下，这个精细调节的机制就会崩溃。事实上，人类和啮齿动物的研究都发现，当内源性昼夜节律与外部线索不一致时，肥胖症和代谢性疾病就会发展。在接下来的综述中，我们将深入探讨营养代谢的昼夜节律性方面的已知知识，并讨论肥胖症作为一种昼夜节律性疾病。
