Nitric Oxide Exerts Basal and Insulin-Dependent Anorexigenic Actions in POMC Hypothalamic Neurons
| Autor: | Denise D. Belsham, Jennifer A. Chalmers, Leigh Wellhauser |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
Nitroprusside 0301 basic medicine endocrine system medicine.medical_specialty Pro-Opiomelanocortin Transcription Genetic medicine.medical_treatment FOXO1 Nitric Oxide Cell Line Nitric oxide Mice 03 medical and health sciences chemistry.chemical_compound Endocrinology Insulin resistance Internal medicine Appetite Depressants medicine Animals Humans Insulin Molecular Biology Original Research Neurons biology Sirtuin 1 digestive oral and skin physiology Arcuate Nucleus of Hypothalamus General Medicine medicine.disease Neuropeptide Y receptor 030104 developmental biology nervous system chemistry Hypothalamus biology.protein hormones hormone substitutes and hormone antagonists Deacetylase activity |
| Zdroj: | Molecular Endocrinology. 30:402-416 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases. Here, we report for the first time that the nitric oxide (NO−) donor, sodium nitroprusside (SNP) mediates anorexigenic actions in both hypothalamic tissue and hypothalamic-derived cell models by mediating the up-regulation of POMC levels. SNP increased POMC mRNA in a dose-dependent manner and enhanced α-melanocortin-secreting hormone production and secretion in mHypoA-POMC/GFP-2 cells. SNP also enhanced insulin-driven POMC expression likely by inhibiting the deacetylase activity of sirtuin 1. Furthermore, SNP enhanced insulin-dependent POMC expression, likely by reducing the transcriptional repression of Foxo1 on the POMC gene. Prolonged SNP exposure prevented the development of insulin resistance. Taken together, the NO− donor SNP enhances the anorexigenic potential of POMC neurons by promoting its transcriptional expression independent and in cooperation with insulin. Thus, increasing cellular NO− levels represents a hormone-independent method of promoting anorexigenic output from the existing POMC neuronal populations and may be advantageous in the fight against these prevalent disorders. |
| Databáze: | OpenAIRE |
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