Leptin Induces Phosphorylation of Neuronal Nitric Oxide Synthase in Defined Hypothalamic Neurons
| Autor: | Renata Frazão, Claudia R. Vianna, Makoto Fukuda, Jose Donato, Carol F. Elias |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Leptin
medicine.medical_specialty Hypothalamus Adipokine Nitric Oxide Synthase Type I Article Mice Endocrinology Arcuate nucleus Internal medicine medicine Animals Phosphorylation In Situ Hybridization Neurons Analysis of Variance biology digestive oral and skin physiology Fasting Immunohistochemistry Nitric oxide synthase Dorsal motor nucleus medicine.anatomical_structure nervous system biology.protein Female Neuron Nucleus hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 151:5415-5427 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2010-0651 |
| Popis: | Studies have indicated that the neurotransmitter nitric oxide (NO) mediates leptin’s effects in the neuroendocrine reproductive axis. However, the neurons involved in these effects and their regulation by leptin is still unknown. We aimed to determine whether NO neurons are direct targets of leptin and by which mechanisms leptin may influence neuronal NO synthase (nNOS) activity. Nicotinamide adenine dinucleotide phosphate diaphorase activity and leptin-induced phosphorylation of signal transducer and activator of transcription-3 immunoreactivity were coexpressed in subsets of neurons of the medial preoptic area, the paraventricular nucleus of the thalamus, the arcuate nucleus (Arc), the dorsomedial nucleus of the hypothalamus (DMH), the posterior hypothalamic area, the ventral premammillary nucleus (PMV), the parabrachial nucleus, and the dorsal motor nucleus of the vagus nerve. Fasting blunted nNOS mRNA expression in the medial preoptic area, Arc, DMH, PMV, and posterior hypothalamic area, and this effect was not restored by acute leptin administration. No difference in the number of neurons expressing nNOS immunoreactivity was noticed comparing hypothalamic sections of fed (wild type and ob/ob), fasted, and fasted leptin-treated mice. However, we found that in states of low leptin levels, as in fasting, or lack of leptin, as in ob/ob mice, the number of neurons expressing the phosphorylated form of nNOS is decreased in the Arc, DMH, and PMV. Notably, acute leptin administration to fasted wild-type mice restored the number of phosphorylated form of nNOS neurons to that observed in fed wild-type mice. Herein we identified the first-order neurons potentially involved in NO-mediated effects of leptin and demonstrate that leptin regulates nNOS activity predominantly through posttranslational mechanisms. |
| Databáze: | OpenAIRE |
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