Intranasal oxytocin reduces weight gain in diet-induced obese prairie voles

Abstract

Oxytocin (OT) elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates and humans by reducing food intake and increasing energy expenditure. In addition to being important in the regulation of energy balance, OT is involved in social behaviors including parent-infant bonds, friendships, and pair bonds. However, the impact of social context on susceptibility to diet-induced obesity (DIO) and feeding behavior (including food sharing) has not been investigated in a rodent model that forms strong social bonds (i.e. prairie vole). Our goals were to determine in Prairie voles (Microtus ochrogaster) whether i) social context impacts susceptibility to DIO and ii) chronic intranasal OT reverses DIO. Voles were housed in divided cages with holes in the divider and paired with a same-sex animal with either the same food [high fat diet (HFD)/HFD, [low fat diet (LFD; chow)/chow], or the opposite food (HFD/chow or chow/HFD) for 19 weeks. HFD-fed voles pair-housed with voles maintained on the HFD demonstrated increased weight relative to pair-housed voles that were both maintained on chow. The study was repeated to determine the impact of social context on DIO susceptibility and body composition when animals are maintained on purified sugar-sweetened HFD and LFD to enhance palatability. As before, we found that voles demonstrated higher weight gain on the HFD/HFD housing paradigm, in part, through increased energy intake and the weight gain was a consequence of an increase in fat mass. However, HFD-fed animals housed with LFD-fed animals (and vice versa) showed intermediate patterns of weight gain and evidence of food sharing. Of translational importance is the finding that chronic intranasal OT appeared to reduce weight gain in DIO voles through a decrease in fat mass with no reduction in lean body mass. These effects were associated with transient reductions in food intake and increased food sharing. These findings identify a role of social context in the pathogenesis of DIO and indicate that chronic intranasal OT treatment reduces weight gain and body fat mass in DIO prairie voles, in part, by reducing food intake.

The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis

“…In addition, acute injections of i.n. OXT over a 7‐day period were able to reduce fasting levels of insulin and also appeared to reduce fasting levels of glucose (not significant) in a DIO prairie vole model . Finally, twice daily s.c. OXT administration over a 4‐week period (0.2 mg kg ‐1 for the initial 2 weeks; 0.4 mg kg ‐1 for the final 2 weeks) decreased fasting blood glucose in a more translational DIO rhesus monkey model .…”

“…Recent studies have shown that central, systemic, or i.n. administration of OXT decreases food intake, weight gain and/or BW in DIO rodents, in genetically obese rodents, in ovariectomised rodents and in a dihydrotestosterone‐induced rat model of polycystic ovary syndrome, as well as in DIO non‐human primates . Below, we review the potential mechanisms that contribute to the effects of chronic OXT in rodent and non‐human primate models of obesity.…”

“…Maejima et al recently compared the effects of chronic s.c. administration of OXT on weight loss in both male and female DIO C57Bl/6J mice and found that OXT reduced BW and fat mass (subcutaneous and visceral) to a similar extent in both sexes. Seelke et al recently reported that female DIO prairie voles may be more sensitive than males to the effects of i.n. OXT on BW although the sample size in this study was small.…”

Effects of peripheral oxytocin administration on body weight, food intake, adipocytes, and biochemical parameters in peri- and postmenopausal female rats

“…Recently, there have been some important discoveries about novel oxytocin functions, particularly its effects on food intake and body weight regulation [15]. Interestingly, as mentioned above, oxytocin was shown to have more marked effects on appetite, body weight, and fat mass in obese animals and humans than in their non-obese counterparts [7,9,10,12,15,16,19]. However, in a cross-sectional study that evaluated the interactions among circulating oxytocin, the menopause, and obesity in pre-and postmenopausal women, it was reported that circulating oxytocin levels were significantly lower in postmenopausal women, especially in obese postmenopausal women, and that circulating oxytocin exhibits significant negative associations with the menopause and body weight [37].…”

“…In addition, these studies suggested that the administration of oxytocin led to a reduction in fat mass by promoting lipolysis in adipose tissue and decreasing the formation of new adipocytes [7,[14][15][16]. Interestingly, these effects of oxytocin on food intake and fat mass were more noticeable in diet-induced and genetically obese rodents [7,17,18], diet-induced obese prairie voles [19], obese rhesus monkeys [9], and obese humans [20][21][22].…”