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Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior.
Endocrinology 156, 1303-1315 (2015)
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Toll-like Receptor-4; Food-intake; Paraventricular Nucleus; Inflammatory Response; Rat Hypothalamus; Body-weight; Microglia; Minocycline; Ghrelin; Obesity
ISSN (print) / ISBN 0013-7227
Quellenangaben Volume: 156, Issue: 4, Pages: 1303-1315
Publisher Endocrine Society
Publishing Place Chevy Chase, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)