Chronic hindbrain administration of oxytocin elicits weight loss in male diet-induced obese mice

Am J Physiol Regul Integr Comp Physiol. 2021 Apr 1;320(4):R471-R487. doi: 10.1152/ajpregu.00294.2020. Epub 2021 Jan 20.

Abstract

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 (TIBAT). 4V OT (1 µg) elevated TIBAT at 0.75 (P = 0.08), 1, and 1.25 h (P < 0.05) postinjection; a higher dose (5 µg) elevated TIBAT 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.

Keywords: brown adipose tissue; obesity; oxytocin; thermogenesis; white adipose tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipocytes, Brown / drug effects
  • Adipocytes, Brown / metabolism
  • Adipocytes, Brown / pathology
  • Adipocytes, White / drug effects
  • Adipocytes, White / metabolism
  • Adipocytes, White / pathology
  • Adiposity / drug effects
  • Animals
  • Anti-Obesity Agents / administration & dosage*
  • Diet, High-Fat*
  • Disease Models, Animal
  • Eating / drug effects
  • Energy Intake / drug effects
  • Infusions, Intraventricular
  • Leptin / blood
  • Male
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / physiopathology
  • Oxytocin / administration & dosage*
  • Rhombencephalon / drug effects*
  • Rhombencephalon / physiopathology
  • Thermogenesis / drug effects
  • Uncoupling Protein 1 / metabolism
  • Weight Loss / drug effects*

Substances

  • Anti-Obesity Agents
  • Leptin
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Oxytocin