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Free keywords:
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/metabolism/physiopathology/prevention & control
Phenotype
Recombinant Fusion Proteins/metabolism
STAT3 Transcription Factor/genetics/*metabolism
*Signal Transduction
Thinness/metabolism/physiopathology
Abstract:
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.
