Nigro Ersilia, Argentino Francesca, Musumeci Giuseppe, Daniele Aurora
Department of Pharmaceutical, Biological, Environmental Sciences and Technologies, University of Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100 Caserta, Italy.
CEINGE-Biotechnologies Advances S.c.a r.l., Via G. Salvatore 486, 80145 Naples, Italy.
Int J Mol Sci. 2025 Sep 15;26(18):8980. doi: 10.3390/ijms26188980.
Orexin is a neuropeptide produced in the hypothalamus that plays a key role in regulating slee-wake cycles, energy metabolism, feeding behavior, and physical activity. It exists in two forms, orexin-A and orexin-B, which bind to G protein-coupled receptors OXR and OXR with differing affinities. Orexin signaling is widespread in the brain and extends to peripheral tissues, including adipose tissue. Its involvement in hypothalamic and extrahypothalamic circuits suggests a broad role in homeostatic regulation. Dysfunctions in the orexinergic system are implicated in neurodegenerative diseases such as Alzheimer's, Parkinson's, and multiple sclerosis, particularly through mechanisms involving sleep disturbances and neuroinflammation. This study examines how orexin influences neural circuits related to arousal, motivation, and motor control. It also explores how physical activity stimulates orexin release, enhancing neuroplasticity and cognitive resilience. In addition, orexin's role in reward-related feeding, genetic susceptibility to obesity, and brown adipose tissue thermogenesis is discussed. Overall, the orexinergic system represents a vital neurochemical link between physical activity, metabolism, and cognitive health. Although many of its mechanisms remain to be clarified, its central role in integrating energy balance and behavioral responses makes it a promising target for future therapeutic strategies.
食欲素是一种在下丘脑中产生的神经肽，在调节睡眠-觉醒周期、能量代谢、进食行为和身体活动方面发挥关键作用。它以两种形式存在，即食欲素-A和食欲素-B，它们以不同的亲和力与G蛋白偶联受体OXR1和OXR2结合。食欲素信号在大脑中广泛存在，并延伸至包括脂肪组织在内的外周组织。它参与下丘脑和下丘脑外回路表明其在稳态调节中具有广泛作用。食欲素能系统功能障碍与阿尔茨海默病、帕金森病和多发性硬化症等神经退行性疾病有关，特别是通过涉及睡眠障碍和神经炎症的机制。本研究考察了食欲素如何影响与觉醒、动机和运动控制相关的神经回路。它还探讨了身体活动如何刺激食欲素释放，增强神经可塑性和认知恢复力。此外，还讨论了食欲素在与奖赏相关的进食、肥胖的遗传易感性以及棕色脂肪组织产热中的作用。总体而言，食欲素能系统代表了身体活动、代谢和认知健康之间至关重要的神经化学联系。尽管其许多机制仍有待阐明，但其在整合能量平衡和行为反应中的核心作用使其成为未来治疗策略的一个有前景的靶点。
