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

Activation of Stat3 signaling in AgRP neurons promotes locomotor activity.

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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.


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.

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