biostudies-literatureShabalina IGForskningsrådet för miljö, areella näringar och samhällsbyggande (FORMAS)the Swedish Research Councilthe European Union Collaborative Project DIABATan unrestricted grant from the 3M Companythe Knut and Alice Wallenberg Foundation1117-28https://www.ebi.ac.uk/biostudies/studies/S-EPMC4830884biostudies-literatureUnknown90(5)The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activArchives of toxicologyMetabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.PMC4830884621-2013-4661216-2012-442278373Shabalina IGNedergaard JCannon BKalinovich AVfalseMetabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activ2016-01-01T00:00:00Z2016 May2025-04-22T11:59:25.404Z2019-03-27T02:11:29ZS-EPMC48308842604112610.1007/s00204-015-1535-4