PDF(Pubmed)
Abstract：
The circadian clock is an endogenous biochemical timing system that coordinates the physiology and behavior of organisms to earth\'s ∼24-hour circadian day/night cycle. The central circadian clock synchronized by environmental cues hierarchically entrains peripheral clocks throughout the body. The circadian system modulates a wide variety of metabolic signaling pathways to maintain whole-body metabolic homeostasis in mammals under changing environmental conditions. Endocrine fibroblast growth factors (FGFs), namely FGF15/19, FGF21, and FGF23, play an important role in regulating systemic metabolism of bile acids, lipids, glucose, proteins, and minerals. Recent evidence indicates that endocrine FGFs function as nutrient sensors that mediate multifactorial interactions between peripheral clocks and energy homeostasis by regulating the expression of metabolic enzymes and hormones. Circadian disruption induced by environmental stressors or genetic ablation is associated with metabolic dysfunction and diurnal disturbances in FGF signaling pathways that contribute to the pathogenesis of metabolic diseases. Time-restricted feeding strengthens the circadian pattern of metabolic signals to improve metabolic health and prevent against metabolic diseases. Chronotherapy, the strategic timing of medication administration to maximize beneficial effects and minimize toxic effects, can provide novel insights into linking biologic rhythms to drug metabolism and toxicity within the therapeutical regimens of diseases. Here we review the circadian regulation of endocrine FGF signaling in whole-body metabolism and the potential effect of circadian dysfunction on the pathogenesis and development of metabolic diseases. We also discuss the potential of chrononutrition and chronotherapy for informing the development of timing interventions with endocrine FGFs to optimize whole-body metabolism in humans. SIGNIFICANCE STATEMENT: The circadian timing system governs physiological, metabolic, and behavioral functions in living organisms. The endocrine fibroblast growth factor (FGF) family (FGF15/19, FGF21, and FGF23) plays an important role in regulating energy and mineral metabolism. Endocrine FGFs function as nutrient sensors that mediate multifactorial interactions between circadian clocks and metabolic homeostasis. Chronic disruption of circadian rhythms increases the risk of metabolic diseases. Chronological interventions such as chrononutrition and chronotherapy provide insights into linking biological rhythms to disease prevention and treatment.
摘要：
昼夜节律时钟是一种内源性生化定时系统，可将生物体的生理和行为协调到地球的〜24小时昼夜节律周期。由环境线索同步的中央昼夜节律时钟分层地夹带整个身体的外围时钟。昼夜节律系统调节多种代谢信号通路以维持哺乳动物在变化的环境条件下的全身代谢稳态。内分泌成纤维细胞生长因子（FGFs），即FGF15/19、FGF21和FGF23，在调节胆汁酸的全身代谢中起重要作用，脂质，葡萄糖，蛋白质和矿物质。最近的证据表明，内分泌FGFs作为营养传感器，通过调节代谢酶和激素的表达来介导外周时钟和能量稳态之间的多因素相互作用。由环境应激源或遗传消融引起的昼夜节律破坏与FGF信号通路中的代谢功能障碍和昼夜紊乱有关，这有助于代谢性疾病的发病机理。限时喂养增强代谢信号的昼夜节律模式，以改善代谢健康并预防代谢疾病。时间疗法,药物管理的战略时机，以最大限度地发挥有益作用和最大限度地减少毒性作用，可以提供新的见解，将生物节律与疾病治疗方案中的药物代谢和毒性联系起来。在这里，我们回顾了内分泌FGF21信号在全身代谢中的昼夜节律调节。昼夜节律功能紊乱在代谢性疾病发生发展中的潜在作用。我们还讨论了时间营养和时间疗法的潜力，以告知内分泌FGFs的定时干预措施的发展，以优化人类的全身代谢。意义声明昼夜节律定时系统支配生理，生物体的代谢和行为功能。内分泌成纤维细胞生长因子（FGF）家族（FGF15/19，FGF21和FGF23）在调节能量和矿物质代谢中起重要作用。内分泌FGFs充当营养传感器，介导昼夜节律和代谢稳态之间的多因素相互作用。昼夜节律的慢性破坏会增加代谢疾病的风险。计时营养和计时疗法等时间干预措施提供了将生物节律与疾病预防和治疗联系起来的见解。
