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To uncover the underlying mechanisms, we employed a controlled exposure system and continuous glucose monitoring (CGM), revealing rapid blood glucose surges and disturbances in energy homeostasis in mice. These effects were attributed to alterations in the hypothalamic transcriptome, specifically impacting insulin and immune response genes, leading to hypothalamic insulin resistance and neuroinflammation. Moreover, benzene exposure activated microglial transcription characterized by heightened expression of IKK\u03b2\/NF-\u03baB-related genes. Remarkably, selective removal of IKK\u03b2 in immune cells or adult microglia in mice alleviated benzene-induced hypothalamic gliosis, and protected against hyperglycemia. In summary, our study uncovers a crucial pathophysiological mechanism, establishing a clear link between airborne toxicant exposure and the onset of metabolic diseases.<\/jats:p>","DOI":"10.1101\/2023.11.08.566279","type":"posted-content","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T18:35:11Z","timestamp":1699900511000},"source":"Crossref","is-referenced-by-count":3,"title":["Microglial NF-\u03baB Signaling Deficiency Protects Against Metabolic Disruptions Caused by Volatile Organic Compound via Modulating the Hypothalamic Transcriptome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9540-4555","authenticated-orcid":false,"given":"L.K.","family":"Debarba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-3011","authenticated-orcid":false,"given":"H.S.M.","family":"Jayarathne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Stilgenbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-1622","authenticated-orcid":false,"given":"A.L.","family":"Terra dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3629-9051","authenticated-orcid":false,"given":"L.","family":"Koshko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3976-7976","authenticated-orcid":false,"given":"S.","family":"Scofield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-7704","authenticated-orcid":false,"given":"U.","family":"Klueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-4612","authenticated-orcid":false,"given":"M.","family":"Sadagurski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023111521550638000_2023.11.08.566279v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2013.01.074"},{"key":"2023111521550638000_2023.11.08.566279v1.2","doi-asserted-by":"publisher","DOI":"10.1177\/2042018819897046"},{"key":"2023111521550638000_2023.11.08.566279v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/atmos11091015"},{"key":"2023111521550638000_2023.11.08.566279v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.155611"},{"key":"2023111521550638000_2023.11.08.566279v1.5","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph14010100"},{"key":"2023111521550638000_2023.11.08.566279v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2014.02.121"},{"key":"2023111521550638000_2023.11.08.566279v1.7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.35371\/kjoem.2011.23.4.387","article-title":"Relationship Between Urinary t, t-muconic Acid and Insulin Resistance in the Elderly","volume":"23","year":"2011","journal-title":"Korean J Occup Environ Med"},{"key":"2023111521550638000_2023.11.08.566279v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwy256"},{"key":"2023111521550638000_2023.11.08.566279v1.9","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16040671"},{"key":"2023111521550638000_2023.11.08.566279v1.10","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-3354-7"},{"key":"2023111521550638000_2023.11.08.566279v1.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183602"},{"key":"2023111521550638000_2023.11.08.566279v1.12","doi-asserted-by":"crossref","unstructured":"Brancati, F. 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