Hindbrain Administration of Oxytocin Reduces Food Intake, Weight Gain and Activates Catecholamine Neurons in the Hindbrain Nucleus of the Solitary Tract in Rats

Abstract

Existing studies show that CNS oxytocin (OT) signaling is important in the control of energy balance, but it is unclear which neurons may contribute to these effects. Our goals were to examine (1) the dose-response effects of acute OT administration into the third (3V; forebrain) and fourth (4V; hindbrain) ventricles to assess sensitivity to OT in forebrain and hindbrain sites, (2) the extent to which chronic 4V administration of OT reduces weight gain associated with the progression of diet-induced obesity, and (3) whether nucleus tractus solitarius (NTS) catecholamine neurons are downstream targets of 4V OT. Initially, we examined the dose-response effects of 3V and 4V OT (0.04, 0.2, 1, or 5 μg). 3V and 4V OT (5 μg) suppressed 0.5-h food intake by 71.7 ± 6.0% and 60 ± 12.9%, respectively. 4V OT (0.04, 0.2, 1 μg) reduced food intake by 30.9 ± 12.9, 42.1 ± 9.4, and 56.4 ± 9.0%, respectively, whereas 3V administration of OT (1 μg) was only effective at reducing 0.5-h food intake by 38.3 ± 10.9%. We subsequently found that chronic 4V OT infusion, as with chronic 3V infusion, reduced body weight gain (specific to fat mass) and tended to reduce plasma leptin in high-fat diet (HFD)-fed rats, in part, through a reduction in energy intake. Lastly, we determined that 4V OT increased the number of hindbrain caudal NTS Fos (+) neurons (156 ± 25) relative to vehicle (12 ± 3). The 4V OT also induced Fos in tyrosine hydroxylase (TH; marker of catecholamine neurons) (+) neurons (25 ± 7%) relative to vehicle (0.8 ± 0.3%). Collectively, these findings support the hypothesis that OT within the hindbrain is effective at reducing food intake, weight gain, and adiposity and that NTS catecholamine neurons in addition to non-catecholaminergic neurons are downstream targets of CNS OT.

The neurohypophyseal hormone oxytocin and eating behaviors: a narrative review

“…Rats with lesions of the PVN, the leading site of OT secretion, exhibited more food intake and weight gain than controls [ 59 ]. In this model, the peripheral and central administration of OT reduced, in a dose-dependent manner, food intake and increased the time intercurrent of the consumption of two consecutive meals [ 60 ]. The results suggest that OT could be involved in the induction and prolongation of satiety.…”

Systematic review: pain, cognition, and cardioprotection—unpacking oxytocin’s contributions in a sport context

“…Food intake behavior is affected by oxytocin, lowering appetite. Oxytocin could offer heart protection from dietary problems, help the regeneration of multiple tissues, and both directly and indirectly reduce obesity, through portion control both in humans [in the hedonic (pleasure-related) and homeostatic (energy balance-related) aspects of feeding] and animals ( Espinoza et al, 2021 ; Mitsui et al, 2011 ; Yokoyama et al, 2009 ; Anekonda et al, 2021 ; Head et al, 2019 ; Nakamura et al, 2011 ; Gosnell and Levine, 2009 ; Lohmeier et al, 2003 ; Shimizu et al, 2016 ; Skinner et al, 2019 ; Yao et al, 2022 ). Admittedly, this needs additional research on humans, particularly dose-response studies, and an understanding of related genetics ( Swarbrick et al, 2011 ).…”

“…In our analysis, we reviewed 32 studies that provided information on injury, pain, and inflammation related to oxytocin. Oxytocin also plays a role in rehabilitation, which is supported by animal studies investigating face/mouth and liver damage (Michelini, 2007a;Michelini, 2007b;Moghimian et al, 2012;ELKady et al, 2021;Jhamandas and MacTavish, 2003;Yokoyama et al, 2009;Moghlmian et al, 2014;Okumura et al, 2019;Xiong et al, 2020;Anekonda et al, 2021). Additionally, oxytocin's recognized anti-inflammatory properties and its ability to facilitate tissue regeneration against oxidative stress have been recognized in rat studies (Wang et al, 2020;Frey Law et al, 2008;González-Hernández et al, 2017;Arabacı Tamer et al, 2020).…”

A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity

“…Another possibility is that individuals with hypothalamic injury lack the ability to respond to intranasal OXT because OXT exerts effects on key hypothalamic nuclei that impact appetite and energy balance. In animal models, however, administration of OXT outside the hypothalamus, in the hindbrain, decreases weight gain via decrease in food intake and also activates catecholamine neurons in nucleus tractus solitarius (NTS) [ 45 ]. Thus, based on the shared physiology governing energy balance, exogenous OXT could plausibly exert effects even in individuals with hypothalamic injury.…”