GLP-1 Receptor Stimulation of the Lateral Parabrachial Nucleus Reduces Food Intake: Neuroanatomical, Electrophysiological, and Behavioral Evidence
| العنوان: | GLP-1 Receptor Stimulation of the Lateral Parabrachial Nucleus Reduces Food Intake: Neuroanatomical, Electrophysiological, and Behavioral Evidence |
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| المؤلفون: | Jennifer E. Richard, Rozita H. Anderberg, Suzanne L. Dickson, Zsolt Liposits, Karolina P. Skibicka, Fredrik Anesten, John-Olov Jansson, Frank Reimann, Imre Farkas, Fiona M. Gribble |
| المصدر: | Endocrinology. 155:4356-4367 |
| بيانات النشر: | The Endocrine Society, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, endocrine system, medicine.medical_specialty, Hypothalamus, Down-Regulation, Mice, Transgenic, Stimulation, Calcitonin gene-related peptide, Biology, Inhibitory postsynaptic potential, Glucagon-Like Peptide-1 Receptor, Rats, Sprague-Dawley, Eating, Mice, Endocrinology, Glucagon-Like Peptide 1, Internal medicine, Receptors, Glucagon, medicine, Animals, Lateral parabrachial nucleus, Neurons, Parabrachial Nucleus, Appetite Regulation, digestive, oral, and skin physiology, Feeding Behavior, Neuroendocrinology, Electrophysiological Phenomena, Rats, Electrophysiology, nervous system, Excitatory postsynaptic potential, Female, hormones, hormone substitutes, and hormone antagonists |
| الوصف: | 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. |
| تدمد: | 1945-7170 0013-7227 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d176b3f7f03bce4774951418f3b05458Test https://doi.org/10.1210/en.2014-1248Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d176b3f7f03bce4774951418f3b05458 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457170 00137227 |
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