Activation of Stat3 signaling in AgRP neurons promotes locomotor activity.
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.
Mesaros
Andrea
A
Department of Mouse Genetics and Metabolism, Institute for Genetics, Center of Molecular Medicine Cologne, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, D-50674 Cologne, Germany.
Koralov
Sergei B
SB
Rother
Eva
E
Wunderlich
F Thomas
FT
Ernst
Marianne B
MB
Barsh
Gregory S
GS
Rajewsky
Klaus
K
Brüning
Jens C
JC
D054369:Agouti-Related Protein / Q000378:metabolism*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001835:Body Weight; D002940:Circadian Rhythm; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013851:Thinness / Q000378:metabolism / Q000503:physiopathology
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D004041:Dietary Fats; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D005947:Glucose