The suprachiasmatic nucleus: a central pacemaker for temporal coordination of energy metabolic homeostasis
摘要
The suprachiasmatic nucleus (SCN) is the principal light-entrained circadian pacemaker in mammals, coordinating daily rhythms in physiology and behavior with the external light–dark cycle. Beyond this canonical role, increasing evidence supports a broader view in which the SCN functions as a central coordinator within a distributed circadian system, helping organize the temporal structure of energy metabolism. Through intercellular coupling, the SCN generates a robust ensemble time signal; through neural, endocrine, and behavioral pathways, it aligns rhythms in feeding, Sleep–wake state, autonomic tone, hormone secretion, body temperature, and peripheral clock phase. From an evolutionary perspective, the strong hierarchical role of the SCN in mammals may have been favored by the need for precise whole-body temporal coordination under the energetic demands of endothermy. However, this hierarchical organization also creates vulnerability: when light exposure, feeding, activity, and Sleep become misaligned, or when SCN network integrity declines, circadian desynchrony can impair metabolic regulation and increase metabolic and cardiometabolic risk.
In this review, we synthesize evolutionary, cellular, circuit, and physiological evidence that positions the SCN as a central pacemaker of temporal metabolic coordination. We argue for a revised model in which the SCN remains hierarchically central but functionally embedded within a distributed clock-metabolism network. We further highlight unresolved questions in SCN cell-type specialization, stress integration, sex differences, biomarker development, and chronotherapeutic design. Understanding how the SCN stabilizes metabolic timing across tissues will be essential for moving from descriptive chronobiology toward mechanism-based circadian medicine.