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

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dc.contributor.authorLee, Chan Heeko
dc.contributor.authorKim, Hyo Jinko
dc.contributor.authorLee, Yong-Sooko
dc.contributor.authorKang, Gil Myoungko
dc.contributor.authorLim, Hyo Sunko
dc.contributor.authorLee, Seung-Hwanko
dc.contributor.authorSong, Do Kyeongko
dc.contributor.authorKwon, Obinko
dc.contributor.authorHwang, Injaeko
dc.contributor.authorSon, Myeongjooko
dc.contributor.authorByun, Kyungheeko
dc.contributor.authorSung, Young Hoonko
dc.contributor.authorKim, Seyunko
dc.contributor.authorKim, Jae Bumko
dc.contributor.authorChoi, Eun Youngko
dc.contributor.authorKim, Young-Bumko
dc.contributor.authorKim, Keetaeko
dc.contributor.authorKweon, Mi-Nako
dc.contributor.authorSohn, Jong-Wooko
dc.contributor.authorKim, Min-Seonko
dc.date.accessioned2018-11-22T06:42:35Z-
dc.date.available2018-11-22T06:42:35Z-
dc.date.created2018-11-13-
dc.date.created2018-11-13-
dc.date.created2018-11-13-
dc.date.created2018-11-13-
dc.date.issued2018-10-
dc.identifier.citationCELL REPORTS, v.25, no.4, pp.934 - +-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10203/246711-
dc.description.abstractObesity-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.-
dc.languageEnglish-
dc.publisherCELL PRESS-
dc.subjectCENTRAL-NERVOUS-SYSTEM-
dc.subjectINSULIN-RESISTANCE-
dc.subjectMYELOID CELLS-
dc.subjectDIET-
dc.subjectMICROGLIA-
dc.subjectDISEASE-
dc.subjectLEPTIN-
dc.subjectCNS-
dc.subjectHETEROGENEITY-
dc.subjectCONSUMPTION-
dc.titleHypothalamic Macrophage Inducible Nitric Oxide Synthase Mediates Obesity-Associated Hypothalamic Inflammation-
dc.typeArticle-
dc.identifier.wosid000448219500012-
dc.identifier.scopusid2-s2.0-85054569910-
dc.type.rimsART-
dc.citation.volume25-
dc.citation.issue4-
dc.citation.beginningpage934-
dc.citation.endingpage+-
dc.citation.publicationnameCELL REPORTS-
dc.identifier.doi10.1016/j.celrep.2018.09.070-
dc.contributor.localauthorKim, Seyun-
dc.contributor.localauthorSohn, Jong-Woo-
dc.contributor.nonIdAuthorKim, Hyo Jin-
dc.contributor.nonIdAuthorLee, Yong-Soo-
dc.contributor.nonIdAuthorKang, Gil Myoung-
dc.contributor.nonIdAuthorLim, Hyo Sun-
dc.contributor.nonIdAuthorLee, Seung-Hwan-
dc.contributor.nonIdAuthorSong, Do Kyeong-
dc.contributor.nonIdAuthorKwon, Obin-
dc.contributor.nonIdAuthorHwang, Injae-
dc.contributor.nonIdAuthorSon, Myeongjoo-
dc.contributor.nonIdAuthorByun, Kyunghee-
dc.contributor.nonIdAuthorSung, Young Hoon-
dc.contributor.nonIdAuthorKim, Jae Bum-
dc.contributor.nonIdAuthorChoi, Eun Young-
dc.contributor.nonIdAuthorKim, Young-Bum-
dc.contributor.nonIdAuthorKim, Keetae-
dc.contributor.nonIdAuthorKweon, Mi-Na-
dc.contributor.nonIdAuthorKim, Min-Seon-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusCENTRAL-NERVOUS-SYSTEM-
dc.subject.keywordPlusINSULIN-RESISTANCE-
dc.subject.keywordPlusMYELOID CELLS-
dc.subject.keywordPlusDIET-
dc.subject.keywordPlusMICROGLIA-
dc.subject.keywordPlusDISEASE-
dc.subject.keywordPlusLEPTIN-
dc.subject.keywordPlusCNS-
dc.subject.keywordPlusHETEROGENEITY-
dc.subject.keywordPlusCONSUMPTION-
dc.subject.keywordPlusCENTRAL-NERVOUS-SYSTEM-
dc.subject.keywordPlusINSULIN-RESISTANCE-
dc.subject.keywordPlusMYELOID CELLS-
dc.subject.keywordPlusDIET-
dc.subject.keywordPlusMICROGLIA-
dc.subject.keywordPlusDISEASE-
dc.subject.keywordPlusLEPTIN-
dc.subject.keywordPlusCNS-
dc.subject.keywordPlusHETEROGENEITY-
dc.subject.keywordPlusCONSUMPTION-
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