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.

Keywords: (Microtus ochrogaster); Intranasal; Obesity; Oxytocin; Prairie vole.

Figure 1.. Social context impacts weight gain in prairie voles maintained on purified HFD or chow.

Adult male and female prairie voles were housed with same-sex voles on same or different diet (HFD or chow) for 19 weeks (N=8–16/group). A-B) Voles gained weight on HFD relative to chow despite having C) reductions in energy intake on HFD relative to chow. Data are expressed as mean ± SEM. *P<0.05 HFD/HFD vs chow/chow; †0.05<P<0.1 HFD/HFD vs. chow/LFD.

Figure 2.. Social context impacts weight gain in prairie voles maintained on purified HFD or LFD.

Adult male and female prairie voles were housed with same-sex voles on same or different diet (HFD or LFD) for 19 weeks (N=4–16/group). A-B) Voles gained weight on HFD relative to LFD through an increase in C) fat mass. These effects occurred through an increase in D) energy intake attributed, in part, to food sharing. Data are expressed as mean ± SEM. Fig. 2B–2D: *P<0.05 HFD/HFD vs. LFD/LFD.

Figure 3.. Picture showing evidence of food sharing between voles in the HFD/LFD social housing condition.

HFD diet (circled) is visible on the side of the LFD subject.

Figure 4.. Correlation of serum leptin with carcass fat mass in the HFD/HFD social housing condition.

There was a significant correlation between serum leptin and carcass fat mass in animals maintained in the HFD/HFD housing paradigm such that carcass fat mass predicted serum leptin levels (r²=0.817; P<0.05).

Figure 5.. Effects of social context on the ability of chronic intranasal OT to impact body weight and body composition in prairie voles maintained on LFD or HFD.

Adult male and female prairie voles were housed with same-sex voles and maintained on a LFD or HFD for 19 weeks prior to treatment onset (N=4–6/group). A) Intranasal OT (8 IU/kg) appeared to reduce body weight and B) body weight gain in DIO voles and these effects were associated with C) reductions in body adiposity; D-F) These effects were not apparent in chow-fed voles Data are expressed as mean ± SEM. †0.05<P<0.1 OT vs. VEH; ††P=0.1 OT vs. VEH.

Figure 6.. Effects of social context on the ability of chronic intranasal OT to impact energy intake in HFD and chow-fed prairie voles.

Adult male and female prairie voles were housed with same-sex voles and maintained on a HFD or chow diet for 19 weeks prior to treatment onset (N=9–12/group). A) Intranasal OT (8 IU/kg) reduced energy intake and/or increased food sharing; B) These effects were not apparent in chow-fed voles. Data are expressed as mean ± SEM. †0.05<P<0.1 OT vs. VEH; ††P=0.1 OT vs. VEH.