The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication

Abstract

Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxytocin neurons in the paraventricular nucleus (PVN) receive neural projections from the arcuate nucleus (ARC), which is an important center for feeding regulation. On the other hand, these neurons in the PVN and supraoptic nucleus project to the ARC. PVN oxytocin neurons also project to the brain stem and the reward-related limbic system. In addition to this, oxytocin induces lipolysis and decreases fat mass. However, these effects in feeding and adipose tissue are known to be dependent on body weight (BW). Oxytocin treatment is more effective in food intake regulation and fat mass decline for individuals with leptin resistance and higher BW, but is known to be less effective in individuals with normal BW. In this review, we present in detail the recent findings on the physiological role of oxytocin in feeding regulation and the anorexigenic neural pathway of oxytocin neurons, as well as the advantage of oxytocin usage for anti-obesity treatment.

Sex and age influence gonadal steroid hormone receptor distributions relative to estrogen receptor β‐containing neurons in the mouse hypothalamic paraventricular nucleus

“…For example, previous reports have shown that ERβ‐containing neurons in the PVN colocalize OT (Oyola et al, 2017), and the expression of OT in these neurons is completely abolished in ERβ knock‐out male mice (Nomura et al, 2002). Functionally, OT is involved in energy balance (Doslikova et al, 2019; Maejima et al, 2018), food intake regulation (Maejima et al, 2018), and sodium (Almeida‐Pereira et al, 2016) balance, processes that, when dysregulated, can contribute to autonomic dysfunction, including hypertension. Thus, the greater number of ERβ‐containing PVN cells in neuroendocrine regions known to express OT neurons suggests a mechanism whereby ERβ may preferentially contribute to autonomic dysfunction in females.…”

Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

“…Three of the remaining five series were used in a single‐labeling immunofluorescence protocol to determine the neurochemical phenotype of PRV‐infected neurons using a subset of neuropeptides clearly associated with energy expenditure. Specifically, in the PVN, we chose to determine the presence of oxytocin (Maejima, Yokota, Nishimori, & Shimomura, ; Ong, Bongiorno, Hernando, & Grill, ), CRH (Deussing & Chen, ; Stengel & Taché, ), and CART (de Lartigue, ; Smedh, Scott, & Moran, ) in PRV‐labeled neurons (Table ). In the PBN, we instead determined the presence of CGRP (Alhadeff, Holland, Nelson, Grill, & De Jonghe, ; Campos et al, ) in PRV‐labeled cells.…”

“…Because of this, we assume that the percentage of double-labeled neurons observed may in fact constitute a minimum, representing a greater actual population of potentially doubly labeled cells (Song, Enquist, & Bartness, 2005) It should also be noted that the neurochemical characterization of PRV-infected cells might in fact under-represent the actual populations, as the PRV is known to shut off host protein synthesis (such as of prepropeptides) in infected cells (Card, 2001;Kim et al, 1999;Strack, Sawyer, Platt, & Loewy, 1989). Given the very large number of neuropeptides known to identify different neuronal subtypes in the brain, we felt it most productive to select for those marking neurons with known involvement in feeding circuits, CGRP (Alhadeff et al, 2015;Campos et al, 2017), oxytocin (Maejima et al, 2018;Ong et al, 2017), CRH (Deussing & Chen, 2018;Stengel & Taché, 2014) and CART (deLartigue 2014, Smedh et al, 2015), with the caveat that the list could not be exhaustive. Furthermore, it has been found that cells can express 10 or more neuropeptides/neurochemicals (Lee, Ryu, & Lee, 2013) and that the proportions can differ based on behavioral, endocrine, physiological, pharmacological, and clinical state (Kiss et al, 1988).…”

“…CART, CRH, and OX were chosen for the study because of their role in energy balance regulation (Lau et al, 2018;Maejima et al, 2018;Zhang et al, 2003). The distribution of these peptides within the PVN was as previously described (Simmons & Swanson, 2009).…”

Role of oxytocin in the control of stress and food intake

“…130,146,159,160 Oxytocin administration has been shown to reduce food intake in laboratory animals and humans. [161][162][163] The anorexigenic effect of oxytocin has been shown to be stronger in diet-induced obese rodents. 164 However, a meta-analysis revealed that the anorexigenic effect of oxytocin administration is not statistically significant in humans.…”