Acute Blockade of PACAP-Dependent Activity in the Ventromedial Nucleus of the Hypothalamus Disrupts Leptin-Induced Behavioral and Molecular Changes in Rats
| العنوان: | Acute Blockade of PACAP-Dependent Activity in the Ventromedial Nucleus of the Hypothalamus Disrupts Leptin-Induced Behavioral and Molecular Changes in Rats |
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| المؤلفون: | SuJean Choi, Matthew M. Hurley, Megan E. Block, Tanya Dabra, Neerali Patel, Matthew Hearing, Riley McCoy, Michael J. Reilly, William Conley, Eden M. Anderson, Christopher Chen, Brian Maunze, Zane Cooper, Evan Hess |
| المصدر: | Neuroendocrinology |
| بيانات النشر: | S. Karger AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Leptin, Male, STAT3 Transcription Factor, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Neuropeptide, 030209 endocrinology & metabolism, Article, Energy homeostasis, 030218 nuclear medicine & medical imaging, Rats, Sprague-Dawley, Eating, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Animals, SOCS3, STAT3, Leptin receptor, Behavior, Animal, biology, Endocrine and Autonomic Systems, Brain-Derived Neurotrophic Factor, digestive, oral, and skin physiology, Rats, Ventromedial nucleus of the hypothalamus, Ventromedial Hypothalamic Nucleus, Hypothalamus, biology.protein, Pituitary Adenylate Cyclase-Activating Polypeptide, hormones, hormone substitutes, and hormone antagonists, Body Temperature Regulation, Signal Transduction |
| الوصف: | Leptin signaling pathways, stemming primarily from the hypothalamus, are necessary for maintaining normal energy homeostasis and body weight. In both rodents and humans, dysregulation of leptin signaling leads to morbid obesity and diabetes. Since leptin resistance is considered a primary factor underlying obesity, understanding the regulation of leptin signaling could lead to therapeutic tools and provide insights into the causality of obesity. While leptin actions in some hypothalamic regions such as the arcuate nuclei have been characterized, less is known about leptin activity in the hypothalamic ventromedial nuclei (VMN). Recently, pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce feeding behavior and alter metabolism when administered into the VMN in a pattern similar to that of leptin. In the current study, we examined whether leptin and PACAP actions in the VMN share overlapping pathways in the regulation of energy balance. Interestingly, PACAP administration into the VMN increased STAT3 phosphorylation and SOCS3 mRNA expression, both of which are hallmarks of leptin receptor activation. In addition, BDNF mRNA expression in the VMN was increased by both leptin and PACAP administration. Moreover, antagonizing PACAP receptors fully reversed the behavioral and cellular effects of leptin injections into the VMN. Electrophysiological studies further illustrated that leptin-induced effects on VMN neurons were blocked by antagonizing PACAP receptors. We conclude that leptin dependency on PACAP signaling in the VMN suggests a potential common signaling cascade, allowing a tonically and systemically secreted neuropeptide to be more precisely regulated by central neuropeptides. |
| تدمد: | 1423-0194 0028-3835 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67a0b94632a6d9c31690ee11b8a6c545 https://doi.org/10.1159/000501337 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....67a0b94632a6d9c31690ee11b8a6c545 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14230194 00283835 |
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