期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 313, 期 4, 页码 R357-R371出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00169.2017
关键词
obesity; brown adipose tissue; thermogenesis; oxytocin
类别
资金
- Office of Research and Development, Medical Research Service, Department of Veterans Affairs (VA)
- VA Puget Sound Health Care System Rodent Metabolic and Behavioral Phenotyping Core
- US Department of Veterans Affairs Biomedical Laboratory Research and Development Service Merit Review Award [5I01BX001213-04]
- University of Washington Nutrition Obesity Research Center Adipose Tissue and Obesity Core
- National Institutes of Health (NIH) Grant [P30 DK-035816]
- University of Washington Diabetes Research Center Vector and Transgenic Mouse Core
- University of Washington Diabetes Research Center Cellular and Molecular Imaging Core
- NIH [P30 DK-017047, DK-095980, HL-091333, HL-107256]
- University of California Office of the President
Oxytocin (OT) administration elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates, and humans by reducing energy intake and increasing energy expenditure. 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 (BAT) through projections to 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 interscapular BAT temperature in 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 and 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 DIO by reducing fat mass. While reduced food intake contributes to this effect, our finding that 4V OT also increases BAT thermogenesis suggests that increased energy expenditure may contribute as well. Collectively, these findings support the hypothesis that, in DIO rats, OT action in the hindbrain evokes sustained weight loss by reducing energy intake and increasing BAT thermogenesis.
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