title: The Environmental Pollutants Perfluorooctane Sulfonate and Perfluorooctanoic Acid Upregulate Uncoupling Protein 1 (UCP1) in Brown-Fat Mitochondria Through a UCP1-Dependent Reduction in Food Intake.
abstract: The environmental pollutants perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) cause a dramatic reduction in the size of the major adipose tissue depots and a general body weight decrease when they are added to the food of mice. We demonstrate here that this is mainly due to a reduction in food intake; this reduction was not due to food aversion. Remarkably and unexpectedly, a large part of the effect of PFOA/PFOS on food intake was dependent on the presence of the uncoupling protein 1 (UCP1) in the mice. Correspondingly, PFOA/PFOS treatment induced recruitment of brown adipose tissue mitochondria: increased oxidative capacity and increased UCP1-mediated oxygen consumption (thermogenesis). In mice pair-fed to the food intake during PFOA/PFOS treatment in wildtype mice, brown-fat mitochondrial recruitment was also induced. We conclude that we have uncovered the existence of a regulatory component of food intake that is dependent upon brown adipose tissue thermogenic activity. The possible environmental consequences of this novel PFOA/PFOS effect (a possible decreased fitness) are noted, as well as the perspectives of this finding on the general understanding of control of food intake control and its possible extension to combatting obesity.
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute;
authors.forename: Irina G
authors.initials: IG
authors.lastname: Shabalina
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute;
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Kramarova
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute;
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Mattsson
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute;
authors.forename: Natasa
authors.initials: N
authors.lastname: Petrovic
authors.affiliation: The Arrhenius Laboratories F3, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden; and.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Rahman Qazi
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute;
authors.forename: Robert I
authors.initials: RI
authors.lastname: Csikasz
authors.affiliation: Medical Department, 3 M Center, St. Paul, Minnesota 55144.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Medical Department, 3 M Center, St. Paul, Minnesota 55144.
authors.forename: John
authors.initials: J
authors.lastname: Butenhoff
authors.affiliation: The Arrhenius Laboratories F3, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden; and.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: DePierre
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute;
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.affiliation: *Department of Molecular Biosciences, The Wenner-Gren Institute; jan.nedergaard@su.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D002149:Energy Intake; D004785:Environmental Pollutants / Q000633:toxicity; D005466:Fluorocarbons / Q000633:toxicity*; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: adipose tissue; body temperature; fatty acid oxidation; food restriction; thermogenesis