title: Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior.
abstract: 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.
authors: Department of Physiology (W.L.R., J.E.S.), Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912; and Helmholtz Diabetes Center (C.-X.Y., Y.G., M.H.T.), Helmholtz Zentrum München and Technische Universität München, Munich 85764, Germany.
authors: Wagner L
authors: WL
authors: Reis
authors: Chun-Xia
authors: CX
authors: Yi
authors: Yuanqing
authors: Y
authors: Gao
authors: Mathias H
authors: MH
authors: Tschöp
authors: Javier E
authors: JE
authors: Stern
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000494:pharmacology; D007113:Immunity, Innate / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D054439:Ghrelin; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4
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