Endogenous Leptin Signaling in the Caudal Nucleus Tractus Solitarius and Area Postrema Is Required for Energy Balance Regulation

Matthew R. Hayes, Karolina P. Skibicka, Theresa M. Leichner, Douglas J. Guarnieri, Ralph J. DiLeone, Kendra K. Bence, Harvey J. Grill

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control.

Original languageEnglish (US)
Pages (from-to)77-83
Number of pages7
JournalCell Metabolism
Volume11
Issue number1
DOIs
StatePublished - Jan 6 2010

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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