Leptin-inhibited PBN Neurons Enhance Responses to Hypoglycemia in Negative Energy Balance

Overview

Journal Nat Neurosci

Date 2014 Nov 11

PMID 25383904

Citations 74

Authors

Jonathan N Flak

Christa M Patterson

Alastair S Garfield

Giuseppe DAgostino

Paulette B Goforth

Ames K Sutton Hickey

Paige A Malec

Jenny-Marie T Wong

Mark Germani

Justin C Jones

Michael Rajala

Leslie Satin

Christopher J Rhodes

David P Olson

Robert T Kennedy

Lora K Heisler

Martin G Myers Jr

Affiliations

Soon will be listed here.

Abstract

Hypoglycemia initiates the counter-regulatory response (CRR), in which the sympathetic nervous system, glucagon and glucocorticoids restore glucose to appropriate concentrations. During starvation, low leptin levels restrain energy utilization, enhancing long-term survival. To ensure short-term survival during hypoglycemia in fasted animals, the CRR must overcome this energy-sparing program and nutrient depletion. Here we identify in mice a previously unrecognized role for leptin and a population of leptin-regulated neurons that modulate the CRR to meet these challenges. Hypoglycemia activates neurons of the parabrachial nucleus (PBN) that coexpress leptin receptor (LepRb) and cholecystokinin (CCK) (PBN LepRb(CCK) neurons), which project to the ventromedial hypothalamic nucleus. Leptin inhibits these cells, and Cck(cre)-mediated ablation of LepRb enhances the CRR. Inhibition of PBN LepRb cells blunts the CRR, whereas their activation mimics the CRR in a CCK-dependent manner. PBN LepRb(CCK) neurons are a crucial component of the CRR system and may be a therapeutic target in hypoglycemia.

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