Hypothalamic Macrophage Inducible Nitric Oxide Synthase Mediates Obesity-Associated Hypothalamic Inflammation

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Obesity-associated metabolic alterations are closely linked to low-grade inflammation in peripheral organs, in which macrophages play a central role. Using genetic labeling of myeloid lineage cells, we show that hypothalamic macrophages normally reside in the perivascular area and circumventricular organ median eminence. Chronic consumption of a high-fat diet (HFD) induces expansion of the monocyte-derived macrophage pool in the hypothalamic arcuate nucleus (ARC), which is significantly attributed to enhanced proliferation of macrophages. Notably, inducible nitric oxide synthase (iNOS) is robustly activated in ARC macrophages of HFD-fed obese mice. Hypothalamic macrophage iNOS inhibition completely abrogates macrophage accumulation and activation, proinflammatory cytokine overproduction, reactive astrogliosis, blood-brain-barrier permeability, and lipid accumulation in the ARC of obese mice. Moreover, central iNOS inhibition improves obesity-induced alterations in systemic glucose metabolism without affecting adiposity. Our findings suggest a critical role for hypothalamic macrophage-expressed iNOS in hypothalamic inflammation and abnormal glucose metabolism in cases of overnutrition-induced obesity.
Publisher
CELL PRESS
Issue Date
2018-10
Language
English
Article Type
Article
Keywords

CENTRAL-NERVOUS-SYSTEM; INSULIN-RESISTANCE; MYELOID CELLS; DIET; MICROGLIA; DISEASE; LEPTIN; CNS; HETEROGENEITY; CONSUMPTION

Citation

CELL REPORTS, v.25, no.4, pp.934 - +

ISSN
2211-1247
DOI
10.1016/j.celrep.2018.09.070
URI
http://hdl.handle.net/10203/246711
Appears in Collection
BS-Journal Papers(저널논문)
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