期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 320, 期 4, 页码 R471-R487出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00294.2020
关键词
brown adipose tissue; obesity; oxytocin; thermogenesis; white adipose tissue
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 Phenotyping Core
- Cellular and Molecular Imaging Core of the Diabetes Research Center at the University of Washington
- National Institutes of Health (NIH) [P30DK017047]
- VA Merit Review Award [5I01BX004102]
- US Department of Veterans Affairs Biomedical Laboratory Research and Development Service
- NIH [5R01DK115976, DK-095980, HL-091333, HL-107256]
- University of California Office of the President
Chronic hindbrain oxytocin (OT) treatment leads to sustained weight loss in diet-induced obese (DIO) mice by reducing energy intake and increasing brown adipose tissue (BAT) thermogenesis at a dosage that does not cause visceral illness.
Previous studies indicate that oxytocin (OT) administration reduces body weight in high-fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake, and body composition. OT reduced body weight by approximately 4.5% +/- 1.4% in DIO mice relative to OT pretreatment body weight (P < 0.05). These effects were associated with reduced adiposity and adipocyte size [inguinal white adipose tissue (IWAT)] (P < 0.05) and attributed, in part, to reduced energy intake (P < 0.05) at a dose that did not increase kaolin intake (P = NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05 < P < 0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature (T-IBAT). 4V OT (1 mg) elevated T-IBAT at 0.75 (P = 0.08), 1, and 1.25 h (P < 0.05) postinjection; a higher dose (5 mg) elevated T-IBAT at 0.75-, 1-, 1.25-, 1.5-, 1.75- (P < 0.05), and 2-h (0.05 < P < 0.1) postinjection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.
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