Obesity in the Mouse Model of Pro-Opiomelanocortin Deficiency Responds to Peripheral Melanocortin

Nat Med. 1999 Sep;5(9):1066-70. doi: 10.1038/12506.

Abstract

Pro-opiomelanocortin (POMC)-derived peptides (the melanocortins adrenocorticotropin, alpha-, beta- and gamma-melanocyte stimulating hormone; and the endogenous opioid beta-endorphin) have a diverse array of biological activities, including roles in pigmentation, adrenocortical function and regulation of energy stores, and in the immune system and the central and peripheral nervous systems. We show here that mice lacking the POMC-derived peptides have obesity, defective adrenal development and altered pigmentation. This phenotype is similar to that of the recently identified human POMC-deficient patients. When treated with a stable alpha-melanocyte-stimulating hormone agonist, mutant mice lost more than 40% of their excess weight after 2 weeks. Our results identify the POMC-null mutant mouse as a model for studying the human POMC-null syndrome, and indicate the therapeutic use of peripheral melanocortin in the treatment of obesity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / pathology
  • Adrenal Glands / physiopathology
  • Adrenocorticotropic Hormone / deficiency
  • Adrenocorticotropic Hormone / genetics
  • Adrenocorticotropic Hormone / metabolism
  • Aldosterone / blood
  • Animals
  • Catecholamines / blood
  • Corticosterone / blood
  • Disease Models, Animal*
  • Female
  • Gene Deletion
  • Hair Color
  • Humans
  • Leptin
  • Mice
  • Obesity / blood
  • Obesity / drug therapy
  • Obesity / physiopathology*
  • Phenotype
  • Pro-Opiomelanocortin / deficiency*
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism
  • Proteins / analysis
  • Weight Loss / drug effects
  • alpha-MSH / agonists
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / pharmacology*
  • alpha-MSH / therapeutic use

Substances

  • Catecholamines
  • Leptin
  • Proteins
  • Aldosterone
  • alpha-MSH
  • Pro-Opiomelanocortin
  • Adrenocorticotropic Hormone
  • Corticosterone