GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake.
ABSTRACT Central glucagon-like-peptide-1 (GLP-1) receptor activation reduces food intake; however, brain nuclei and mechanism(s) mediating this effect remain poorly understood. Although central nervous system GLP-1 is produced almost exclusively in the nucleus of the solitary tract in the hindbrain, GLP-1 receptors (GLP-1R) are expressed throughout the brain, including nuclei in the mesolimbic reward system (MRS), e.g. the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Here, we examine the MRS as a potential site of action for GLP-1-mediated control of food intake and body weight. Double immunohistochemistry for Fluorogold (monosynaptic retrograde tracer) and GLP-1 neuron immunoreactivity indicated that GLP-1-producing nucleus tractus solitarius neurons project directly to the VTA, the NAc core, and the NAc shell. Pharmacological data showed that GLP-1R activation in the VTA, NAc core, and NAc shell decreased food intake, especially of highly-palatable foods, and body weight. Moreover, blockade of endogenous GLP-1R signaling in the VTA and NAc core resulted in a significant increase in food intake, establishing a physiological relevance for GLP-1 signaling in the MRS. Current data highlight these nuclei within the MRS as novel sites for GLP-1R-mediated control of food intake and body weight.
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ABSTRACT: Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD). In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD.Frontiers in neuroscience. 01/2014; 8:288.
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ABSTRACT: 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, as 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-1R) 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 two energy balance regulating peptides, calcitonin gene related peptide (CGRP) and interleukin-6. Moreover, nearly seventy percent 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.Endocrinology 08/2014; · 4.72 Impact Factor
- Frontiers in Endocrinology 01/2014; 5:117.