Chronic Hindbrain Administration of Oxytocin is Sufficient to Elicit Weight Loss in Diet-Induced Obese Rats

Oxytocin (OT) administration elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates and humans by both reducing energy intake and increasing energy expenditure (EE). Although the neurocircuitry underlying these effects remains uncertain, OT neurons in the paraventricular nucleus are positioned to control both energy intake and sympathetic nervous system outflow to interscapular brown adipose tissue (IBAT) through projections to both the hindbrain nucleus of the solitary tract and spinal cord. The current work was undertaken to examine whether central OT increases BAT thermogenesis, whether this effect involves hindbrain OT receptors (OTRs), and whether such effects are associated with sustained weight loss following chronic administration. To assess OT-elicited changes in BAT thermogenesis, we measured the effects of intracerebroventricular administration of OT on IBAT temperature (TIBAT) in both rats and mice. Because fourth ventricular (4V) infusion targets hindbrain OTRs, whereas third ventricular (3V) administration targets both forebrain and hindbrain OTRs, we compared responses to OT following chronic 3V infusion in DIO rats and mice with chronic 4V infusion in DIO rats. We report that chronic 4V infusion of OT into two distinct rat models recapitulates the effects of 3V OT to ameliorate diet-induced obesity by reducing fat mass. While reduced food intake contributes to this effect, our finding that 4V OT also increases BAT thermogenesis suggests that increased EE may contribute as well. These findings collectively support the hypothesis that in DIO rats, OT action in the hindbrain evokes sustained weight loss by both reducing energy intake and increasing BAT thermogenesis.

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