GLP-1 Receptor Stimulation of the Lateral Parabrachial Nucleus Reduces Food Intake: Neuroanatomical, Electrophysiological, and Behavioral Evidence

被引:77
作者
Richard, Jennifer E. [1 ]
Farkas, Imre [2 ]
Anesten, Fredrik [3 ]
Anderberg, Rozita H. [1 ]
Dickson, Suzanne L. [3 ]
Gribble, Fiona M. [4 ,5 ]
Reimann, Frank [4 ,5 ]
Jansson, John-Olov [3 ]
Liposits, Zsolt [2 ]
Skibicka, Karolina P. [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Metab Phys, SE-40530 Gothenburg, Sweden
[2] Inst Expt Med, Lab Endocrine Neurobiol, H-1083 Budapest, Hungary
[3] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, SE-40530 Gothenburg, Sweden
[4] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England
[5] Univ Cambridge, Wellcome Trust, MRC, Inst Metab Sci, Cambridge CB2 2XY, England
基金
瑞典研究理事会; 英国惠康基金; 匈牙利科学研究基金会;
关键词
GLUCAGON-LIKE PEPTIDE-1; BRAIN-STEM; SOLITARY TRACT; TASTE PATHWAYS; NEURONS; RAT; ACCUMBENS; MICE; CHOLECYSTOKININ; INTERLEUKIN-6;
D O I
10.1210/en.2014-1248
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN.
引用
收藏
页码:4356 / 4367
页数:12
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