Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility

Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3155-60. doi: 10.1073/pnas.1120501109. Epub 2012 Jan 9.


Leptin-deficient (Lep(ob/ob)) mice are obese, diabetic, and infertile. Ablation of neurons that make agouti-related protein (AgRP) in moderately obese adult Lep(ob/ob) mice caused severe anorexia. The mice stopped eating for 2 wk and then gradually recovered. Their body weight fell to within a normal range for WT mice, at which point food intake and glucose tolerance were restored to that of WT mice. Remarkably, both male and female Lep(ob/ob) mice became fertile. Ablation of neurons that express melanin-concentrating hormone (MCH) in adult Lep(ob/ob) mice had no effect on food intake, body weight, or fertility, but resulted in improved glucose tolerance. We conclude that AgRP-expressing neurons play a critical role in mediating the metabolic syndrome and infertility of Lep(ob/ob) mice, whereas MCH-expressing neurons have only a minor role.

Publication types

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

MeSH terms

  • Agouti-Related Protein / metabolism*
  • Animals
  • Body Weight / physiology
  • Feeding Behavior / physiology
  • Fertility / physiology*
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Homeostasis
  • Hypothalamic Hormones / metabolism*
  • Leptin / deficiency*
  • Leptin / metabolism
  • Melanins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Neurons / metabolism*
  • Neurons / pathology*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Pituitary Hormones / metabolism*
  • Survival Analysis


  • Agouti-Related Protein
  • Hypothalamic Hormones
  • Leptin
  • Melanins
  • Pituitary Hormones
  • melanin-concentrating hormone
  • Glucose