Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

Abstract

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.

Oxytocin in survivors of childhood-onset craniopharyngioma

“…It is already well established that the hypothalamus is the regulatory center for feeding and satiety [26]. Oxytocin has also been linked to energy homeostasis mechanisms in animals, where it acts as a strong inhibitor of food intake and affects energy expenditure and glucose homeostasis [27][28][29][30][31]. Oxytocin has also been shown to play an important role in metabolism and energy balance in humans [32,33], such as reducing caloric intake with a preferential effect on fat intake [11] and reward-driven food intake in humans [34].…”

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

“…Recognizing that oxytocin inhibits weight gain in rodent models [21,41] and in humans [29], we challenged oxytocin-deficient B6;129S-Oxttm1Wsy/J mutant mice with canine source L. reuteri 2546 to determine whether this neurotropic hormone oxytocin is essential for L. reuteri 2546-induced weight control. We found that mice globally lacking oxytocin did not benefit from microbe-induced body weight Figures 5C and 5D).…”

“…Importantly, oxytocin has also been convincingly linked with protection from obesity [17][18][19][20][21][22][23]. While the nonapeptide oxytocin is historically recognized for its role in parturition [24] and lactation [25] it has gained more recent attention for its apparent effects on prosocial behavior [26,27] and therapeutic potential in the treatment of autism spectrum disorder (ASD) [26,27], schizophrenia [26,28] and obesity [17][18][19][20][21][22][23]. A large number of ongoing investigations in humans list oxytocin as the focus in studies on caloric intake, gastric emptying, or obesity, as displayed in the ClinicalTrials.…”

Neuroendocrine control of satiation

“…Mice lacking oxytocin or oxytocin receptors develop late-onset obesity with little changes in daily food intake [351][352][353], and pair-feeding studies confirm that reductions in eating only partially account for oxytocin's effect on body weight, suggesting that oxytocin also controls energy expenditure [354,355].…”