Lipopolysaccharide inhibits ghrelin-excited neurons of the arcuate nucleus and reduces food intake via central nitric oxide signaling
| Autor: | Sarah Pinkernell, Tito Borner, Thomas Riediger, Thomas A. Lutz |
|---|---|
| Přispěvatelé: | University of Zurich, Riediger, Thomas |
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male Benzylamines Amidines Nitric Oxide Synthase Type II Stimulation Energy homeostasis Behavioral Neuroscience chemistry.chemical_compound Eating 0302 clinical medicine 2802 Behavioral Neuroscience Premovement neuronal activity Enzyme Inhibitors Phosphorylation Cyclic GMP 2. Zero hunger Neurons 0303 health sciences biology 10081 Institute of Veterinary Physiology Immunohistochemistry Ghrelin 3. Good health Anorexia Nitric oxide synthase 2807 Endocrine and Autonomic Systems STAT1 Transcription Factor Hypothalamus 10076 Center for Integrative Human Physiology lipids (amino acids peptides and proteins) medicine.drug Signal Transduction medicine.medical_specialty Immunology 610 Medicine & health Nitric Oxide Nitric oxide 03 medical and health sciences Internal medicine Orexigenic medicine Animals Rats Wistar 030304 developmental biology Injections Intraventricular 2403 Immunology Endocrine and Autonomic Systems Arcuate Nucleus of Hypothalamus Electrophysiological Phenomena Rats Endocrinology chemistry biology.protein 570 Life sciences 030217 neurology & neurosurgery |
| Zdroj: | Brain Behavior and Immunity Brain behavior and immunity |
| ISSN: | 1090-2139 |
| Popis: | Lipopolysaccharide (LPS) induces anorexia and expression of inducible nitric oxide synthase (iNOS) in the hypothalamic arcuate nucleus (Arc). Peripheral administration of the iNOS inhibitor 1400 W counteracts the anorectic effects of LPS. Here we investigated the role of central NO signaling in LPS anorexia. In electrophysiological studies we tested whether 1400 W counteracts the iNOS-dependent inhibition of Arc neurons triggered by in vivo or in vitro stimulation with LPS. We used the hormone ghrelin as a functional reference stimulus because ghrelin is known to activate orexigenic Arc neurons. Further, we investigated whether in vitro LPS stimulation induces an iNOS-mediated formation of the second messenger cGMP. Since the STAT1 pathway contributes to the regulation of iNOS expression we investigated whether LPS treatment induces STAT1 phosphorylation in the Arc. Finally we tested the effect of intracerebroventricular injection of 1400 W on LPS-induced anorexia. Superfusion with 1400 W (10(-4) M) increased neuronal activity in 37% of neurons in Arc slices from LPS treated (100 μg/kg ip) but not from saline treated rats. Similarly, 1400 W excited 45% of Arc neurons after in vitro stimulation with LPS (100 ng/ml). In both approaches, a considerable percentage of 1400 W sensitive neurons were excited by ghrelin (10(-8)M; 50% and 75%, respectively). In vitro stimulation with LPS induced cGMP formation in the Arc, which was blocked by co-incubation with 1400 W. LPS treatment elicited a pSTAT1 response in the Arc of mice. Central 1400 W injection (4 μg/rat) attenuated LPS-induced anorexia and counteracted the LPS-dependent decrease in respiratory quotient and energy expenditure. In conclusion, the current findings substantiate a role of central iNOS dependent NO formation in LPS-induced effects on eating and energy homeostasis. A pharmacological blockade of NO formation might be a therapeutic approach to ameliorate disease-related anorexia. |
| Databáze: | OpenAIRE |
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