Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior
| Autor: | M. H. Tschöp, Javier E. Stern, Wagner Luis Reis, Chun-Xia Yi, Yuanqing Gao |
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| Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Patch-Clamp Techniques Biology Corrections Endocrinology Proopiomelanocortin Arcuate nucleus Orexigenic Internal medicine medicine Premovement neuronal activity Animals Agouti-Related Protein Neuropeptide Y Rats Wistar Neurons Arc (protein) Microglia Energy Balance-Obesity digestive oral and skin physiology Arcuate Nucleus of Hypothalamus Feeding Behavior Neuropeptide Y receptor Ghrelin Immunity Innate Rats Toll-Like Receptor 4 medicine.anatomical_structure nervous system biology.protein medicine.drug Signal Transduction |
| Zdroj: | Endocrinology 156, 1303-1315 (2015) Endocrinology, 156(4), 1303-1315. The Endocrine Society |
| ISSN: | 0013-7227 |
| Popis: | Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior. |
| Databáze: | OpenAIRE |
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