Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility

Cell Metab. 2010 Apr 7;11(4):286-97. doi: 10.1016/j.cmet.2010.03.002.


Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Lepr(flox/flox) IR(flox/flox) mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Lepr(flox/flox) IR(flox/flox) female mice display elevated serum testosterone levels and ovarian abnormalities, resulting in reduced fertility. We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Glucose / metabolism*
  • Female
  • Fertility / physiology*
  • Homeostasis / physiology*
  • Hypothalamus / cytology
  • Hypothalamus / metabolism*
  • Insulin / metabolism*
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Leptin / metabolism*
  • Male
  • Mice
  • Neurons / metabolism*
  • Pro-Opiomelanocortin / metabolism
  • Testosterone / blood


  • Blood Glucose
  • Insulin
  • Leptin
  • Testosterone
  • Pro-Opiomelanocortin