Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 308, Issue 5, Pages R431-R438Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00441.2014
Keywords
obesity; food intake; energy expenditure; oxytocin
Categories
Funding
- Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA)
- California National Primate Research Center (CNPRC) Pilot Award [0D011107]
- Department of VA Merit Review Research Program
- National Institutes of Health [DK-095980, HL-091333, HL-107256]
- University of California Office of the President
- VA Senior Research Career Scientist award
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Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2 x daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 +/- 0.4% (approximate to 0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 +/- 7% (P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 +/- 5% (P < 0.05) and 8-h fructose-sweetened beverage intake by 18 +/- 8% (P < 0.05). OT increased EE during the dark cycle by 14 +/- 3% (P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis.
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