Low sympathetic tone and obese phenotype in oxytocin-deficient mice

Obesity (Silver Spring). 2009 May;17(5):980-4. doi: 10.1038/oby.2009.12. Epub 2009 Feb 26.


Oxytocin (Oxt) is secreted both peripherally and centrally and is involved in several functions including parturition, milk let-down reflex, social behavior, and food intake. Recently, it has been shown that mice deficient in Oxt receptor develop late-onset obesity. In this study, we characterized a murin model deficient in Oxt peptide (Oxt(-/-)) to evaluate food intake and body weight, glucose tolerance and insulin tolerance, leptin and adrenaline levels. We found that Oxt(-/-) mice develop late-onset obesity and hyperleptinemia without any alterations in food intake in addition to having a decreased insulin sensitivity and glucose intolerance. The lack of Oxt in our murin model also results in lower adrenalin levels which led us to hypothesize that the metabolic changes observed are associated with a decreased sympathetic nervous tone. It has been shown that Oxt neurons in the paraventricular nucleus (PVN) are a component of a leptin-sensitive signaling circuit between the hypothalamus and caudal brain stem for the regulation of food intake and energy homeostasis. Nevertheless, the lack of Oxt in these mice does not have a direct impact on feeding behavior whose regulation is probably dependent on the complex interplay of several factors. The lack of hyperphagia evident in the Oxt(-/-) mice may, in part, be attributed to the developmental compensation of other satiety factors such as cholecystokinin or bombesin-related peptides which merits further investigation. These findings identify Oxt as an important central regulator of energy homeostasis.

MeSH terms

  • Adipose Tissue / anatomy & histology
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight
  • Brain Stem / physiology
  • Brain Stem / physiopathology
  • Crosses, Genetic
  • Energy Intake / genetics*
  • Glucose Intolerance / genetics
  • Hypothalamus / physiology
  • Hypothalamus / physiopathology
  • Insulin / physiology
  • Insulin / therapeutic use
  • Leptin / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / genetics
  • Obesity / physiopathology*
  • Oxytocin / deficiency*
  • Signal Transduction / physiology
  • Stomach / anatomy & histology
  • Sympathetic Nervous System / physiopathology*


  • Blood Glucose
  • Insulin
  • Leptin
  • Oxytocin