Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Division of Pediatric Endocrinology, Massachusetts General Hospital for Children, Boston, MA 02114, USA.
Int J Mol Sci. 2021 Jul 20;22(14):7737. doi: 10.3390/ijms22147737.
The hypothalamic peptide oxytocin and its receptor are involved in a range of physiological processes, including parturition, lactation, cell growth, wound healing, and social behavior. More recently, increasing evidence has established the effects of oxytocin on food intake, energy expenditure, and peripheral metabolism. In this review, we provide a comprehensive description of the central oxytocinergic system in which oxytocin acts to shape eating behavior and metabolism. Next, we discuss the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization. A brief summary of oxytocin actions learned from animal models is presented, showing that weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis. Following an in-depth discussion on the technical challenges related to endogenous oxytocin measurements in humans, we synthesize data related to the association between endogenous oxytocin levels, weight status, metabolic syndrome, and bone health. We then review clinical trials showing that in humans, acute oxytocin administration reduces food intake, attenuates fMRI activation of food motivation brain areas, and increases activation of self-control brain regions. Further strengthening the role of oxytocin in appetite regulation, we review conditions of hypothalamic insult and certain genetic pathologies associated with oxytocin depletion that present with hyperphagia, extreme weight gain, and poor metabolic profile. Intranasal oxytocin is currently being evaluated in human clinical trials to learn whether oxytocin-based therapeutics can be used to treat obesity and its associated sequela. At the end of this review, we address the fundamental challenges that remain in translating this line of research to clinical care.
下丘脑肽催产素及其受体参与一系列生理过程，包括分娩、哺乳、细胞生长、伤口愈合和社会行为。最近，越来越多的证据表明催产素对食物摄入、能量消耗和外周代谢有影响。在这篇综述中，我们全面描述了催产素作用于进食行为和代谢的中枢催产素能系统。接下来，我们讨论了催产素对关键代谢器官的外周有益作用，包括抑制内脏脂肪组织炎症、骨骼肌再生和骨组织矿化。简要总结了从动物模型中获得的关于催产素作用的知识，表明慢性催产素治疗引起的体重减轻不仅与它的厌食作用有关，还与随之而来的能量消耗增加和脂肪分解有关。在深入讨论了与人类内源性催产素测量相关的技术挑战之后，我们综合了与内源性催产素水平、体重状况、代谢综合征和骨骼健康相关的数据。然后，我们回顾了临床试验，表明在人类中，急性催产素给药可减少食物摄入，减弱 fMRI 对食物动机脑区的激活，并增加自我控制脑区的激活。进一步加强了催产素在食欲调节中的作用，我们回顾了下丘脑损伤和某些与催产素耗竭相关的遗传病理条件，这些条件表现为食欲过盛、体重极度增加和代谢状况不佳。鼻内催产素目前正在人类临床试验中进行评估，以了解基于催产素的治疗方法是否可用于治疗肥胖及其相关后遗症。在这篇综述的最后，我们讨论了将这一研究领域转化为临床护理所面临的基本挑战。
