Activation of Stat3 signaling in AgRP neurons promotes locomotor activity

Cell Metab. 2008 Mar;7(3):236-48. doi: 10.1016/j.cmet.2008.01.007.


Leptin, an adipocyte-derived hormone, acts on hypothalamic neurons located in the arcuate nucleus (ARC) of the hypothalamus to regulate energy homeostasis. One of the leptin-regulated neuronal subtypes in the ARC are agouti-related peptide (AgRP)-expressing neurons, which are involved in the regulation of food intake and are directly inhibited by leptin. Leptin activates the signal transducer and activator of transcription 3 (Stat3), but the role of Stat3 in the regulation of AgRP neurons is unclear. Here we show that mice expressing a constitutively active version of Stat3 selectively in AgRP neurons are lean and exhibit relative resistance to diet-induced obesity. Surprisingly, this phenotype arises from increased locomotor activity in the presence of unaltered AgRP expression. These data demonstrate that Stat3-dependent signaling in AgRP neurons in the ARC controls locomotor activity independently of AgRP regulation.

Publication types

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

MeSH terms

  • Agouti-Related Protein / metabolism*
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Body Weight
  • Circadian Rhythm
  • Dietary Fats / administration & dosage
  • Disease Models, Animal
  • Eating
  • Energy Metabolism
  • Female
  • Genotype
  • Glucose / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity*
  • Mutation
  • Neurons / metabolism*
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Obesity / prevention & control
  • Phenotype
  • Recombinant Fusion Proteins / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*
  • Thinness / metabolism
  • Thinness / physiopathology


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Dietary Fats
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • Glucose