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Human epidemiological studies support arsenic exposure as a risk factor for T2D, although the precise mechanism is unclear. We hypothesized that chronic arsenic ingestion alters glucose homeostasis by impairing adaptive thermogenesis, i.e., body heat production in cold environments. Arsenic is a pervasive environmental contaminant, with more than 200 million people worldwide currently exposed to arsenic-contaminated drinking water. Male C57BL\/6J mice exposed to sodium arsenite in drinking water at 300 \u03bcg\/L for 9 wk experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass and subcutaneous inguinal white adipose tissue (iWAT) mass. RNA sequencing analysis of iWAT indicated that arsenic dysregulated mitochondrial processes, including fatty acid metabolism. Western blotting in WAT confirmed that arsenic significantly decreased TOMM20, a correlate of mitochondrial abundance; PGC1A, a master regulator of mitochondrial biogenesis; and, CPT1B, the rate-limiting step of fatty acid oxidation (FAO). Our findings show that chronic arsenic exposure impacts the mitochondrial proteins of thermogenic tissues involved in energy expenditure and substrate regulation, providing novel mechanistic evidence for arsenic\u2019s role in T2D development.<\/jats:p>","DOI":"10.1152\/ajpendo.00282.2019","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T15:22:06Z","timestamp":1581434526000},"page":"E667-E677","source":"Crossref","is-referenced-by-count":16,"title":["Chronic arsenic exposure impairs adaptive thermogenesis in male C57BL\/6J mice"],"prefix":"10.1152","volume":"318","author":[{"given":"Felicia","family":"Castriota","sequence":"first","affiliation":[{"name":"Superfund Research Program, University of California, Berkeley, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter-James H.","family":"Zushin","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology, University of California, 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