NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates

Science. 2005 Oct 28;310(5748):683-5. doi: 10.1126/science.1115524.


Hypothalamic neurons that express neuropeptide Y (NPY) and agouti-related protein (AgRP) are thought to be critical regulators of feeding behavior and body weight. To determine whether NPY/AgRP neurons are essential in mice, we targeted the human diphtheria toxin receptor to the Agrp locus, which allows temporally controlled ablation of NPY/AgRP neurons to occur after an injection of diphtheria toxin. Neonatal ablation of NPY/AgRP neurons had minimal effects on feeding, whereas their ablation in adults caused rapid starvation. These results suggest that network-based compensatory mechanisms can develop after the ablation of NPY/AgRP neurons in neonates but do not readily occur when these neurons become essential in adults.

MeSH terms

  • Aging / physiology
  • Agouti-Related Protein
  • Animals
  • Animals, Newborn
  • Arcuate Nucleus of Hypothalamus / cytology
  • Body Weight / physiology
  • Diphtheria Toxin
  • Feeding Behavior / physiology*
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Neurons / metabolism
  • Neurons / physiology*
  • Neuropeptide Y / metabolism*
  • Proteins / metabolism*
  • Receptors, Cell Surface / genetics


  • AGRP protein, human
  • Agouti-Related Protein
  • Agrp protein, mouse
  • Diphtheria Toxin
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptide Y
  • Proteins
  • Receptors, Cell Surface