title: UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic.
abstract: The phenomenon of white fat "browning," in which certain white adipose tissue depots significantly increase gene expression for the uncoupling protein UCP1 and thus supposedly acquire thermogenic, fat-burning properties, has attracted considerable attention. Because the mRNA increases are from very low initial levels, the metabolic relevance of the change is unclear: is the UCP1 protein thermogenically competent in these brite/beige-fat mitochondria? We found that, in mitochondria isolated from the inguinal "white" adipose depot of cold-acclimated mice, UCP1 protein levels almost reached those in brown-fat mitochondria. The UCP1 was thermogenically functional, in that these mitochondria exhibited UCP1-dependent thermogenesis with lipid or carbohydrate substrates with canonical guanosine diphosphate (GDP) sensitivity and loss of thermogenesis in UCP1 knockout (KO) mice. Obesogenic mouse strains had a lower thermogenic potential than obesity-resistant strains. The thermogenic density (UCP1-dependent oxygen consumption per g tissue) of inguinal white adipose tissue was maximally one-fifth of interscapular brown adipose tissue, and the total quantitative contribution of all inguinal mitochondria was maximally one-third of all interscapular brown-fat mitochondria, indicating that the classical brown adipose tissue depots would still predominate in thermogenesis.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Shabalina
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Natasa
authors.initials: N
authors.lastname: Petrovic
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Jasper M A
authors.initials: JM
authors.lastname: de Jong
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Kalinovich
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden. Electronic address: jan@metabol.su.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D050260:Carbohydrate Metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D006153:Guanosine Diphosphate