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Several studies demonstrated a correlation between exposure to volatile organic compounds (VOCs) in indoor\/outdoor environments and T2D. Here, we conducted the first meta-analysis, establishing a robust association between exposure to benzene, a prevalent airborne VOC, and insulin resistance in humans across all ages. We used a controlled benzene exposure system, continuous glucose monitoring approach, and indirect calorimetry in mice, to investigate the underlying mechanisms. Following exposure, disruptions in energy homeostasis, accompanied by modifications in the hypothalamic transcriptome and alterations in insulin and immune signaling, were observed exclusively in males, leading to a surge in blood glucose levels. In agreement, RNA sequencing of microglia revealed increased expression of genes associated with immune response and NF-\u03baB signaling. Selective ablation of IKK\u03b2 in immune cells (Cx3cr1GFP\u0394IKK) or exclusively in microglia (Tmem119ER\u0394IKK) in adult mice alleviated benzene-induced gliosis, restored energy homeostasis and hypothalamic gene expression, and protected against hyperglycemia. We conclude that the microglial NF-\u03baB pathway plays a critical role in chemical-induced metabolic disturbances, revealing a vital pathophysiological mechanism linking exposure to airborne toxicants and the onset of metabolic diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db24-0110","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T11:48:36Z","timestamp":1727264916000},"page":"2065-2077","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":18,"title":["Microglia Mediate Metabolic Dysfunction From Common Air Pollutants Through NF-\u03baB Signaling"],"prefix":"10.2337","volume":"73","author":[{"given":"Lucas K.","family":"Debarba","sequence":"first","affiliation":[{"name":"1Department of Biological Sciences, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hashan S.M.","family":"Jayarathne","sequence":"additional","affiliation":[{"name":"1Department of Biological Sciences, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Stilgenbauer","sequence":"additional","affiliation":[{"name":"1Department of Biological Sciences, Wayne State University, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L. 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