Cited 27 time in webofscience Cited 29 time in scopus

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

Title
Hypothalamic Macrophage Inducible Nitric Oxide Synthase Mediates Obesity-Associated Hypothalamic Inflammation
Authors
Lee, Chan HeeKim, Hyo JinLee, Yong SooKang, Gil MyoungLim, Hyo SunLee, Seung HwanSong, Do KyeongKwon, ObinHwang, InjaeSon, MyeongjooByun, KyungheeSung, Young HoonKim, SeyunKim, Jae BumChoi, Eun YoungKim, Young BumKim, KeetaeKweon, Mi NaSohn, Jong WooKim, Min Seon
DGIST Authors
Kim, Keetae
Issue Date
2018-10
Citation
Cell Reports, 25(4), 934-946.e5
Type
Article
Article Type
Article
ISSN
2211-1247
Abstract
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. Lee et al. demonstrate in mice that, upon prolonged high-fat diet feeding, hypothalamic macrophages proliferate, expand their pool, and sustain hypothalamic inflammation. Moreover, they show that hypothalamic macrophage iNOS inhibition diminishes macrophage activation, astrogliosis, blood-brain-barrier permeability, and impaired glucose metabolism in diet-induced obese mice. © 2018 The Authors
URI
http://hdl.handle.net/20.500.11750/9364
DOI
10.1016/j.celrep.2018.09.070
Publisher
Cell Press
Files:
There are no files associated with this item.
Collection:
Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles


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