Abstract
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.
Highlights
The neuropeptide oxytocin and its receptor are well-documented for orchestrating a broad repertoire of physiological processes across species
We describe the distribution of oxytocin and its receptor in the central nervous system (CNS) as a framework to mechanistically explain the involvement of oxytocin in eating behavior and energy balance
We focus on interventional human studies assessing the effects of oxytocin on food intake, neurobiological processing of food stimuli, and metabolism
Summary
The neuropeptide oxytocin and its receptor are well-documented for orchestrating a broad repertoire of physiological processes across species. In addition to the brain areas delineated above to which the oxytocin neurons send their projections (i.e., ARC, VTA, NAc, NST, amygdala), the oxytocin receptor is found in other brain areas [6,53] that are involved in the cognitive perception and reward value determination of food, potentially linking meal-related gut input and peripheral signals of energy bioavailability arriving at the hypothalamus with higher order brain input to regulate complex eating behaviors These areas include the insular cortex [4], which functions as a multisensory gustatory neural hub [56]; the hippocampus [57], which plays an important role in goal-directed behavior, memory, and decision-making [58]; and the prefrontal cortex and anterior cingulate cortex, which are involved in attentional as well as cognitive control [34,59,60,61,62]. The neuroanatomical circuits of the oxytocin system provide a framework in which a mechanistic explanation for oxytocin participation in eating behavior can be formed
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