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Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation.

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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Hayes MR,Skibicka KP,Leichner TM,Guarnieri DJ,DiLeone RJ,Bence KK,Grill HJ

doi

10.1016/j.cmet.2009.10.009

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

77-83

issue

1

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(09)00335-0

journal_volume

11

pub_type

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