title: UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice.
abstract: Apart from UCP1-based nonshivering thermogenesis in brown adipocytes, the identity of thermogenic mechanisms that can be activated to reduce a positive energy balance is largely unknown. To identify potentially useful mechanisms, we have analyzed physiological and molecular mechanisms that enable mice, genetically deficient in UCP1 and sensitive to acute exposure to the cold at 4 degrees C, to adapt to long term exposure at 4 degrees C. UCP1-deficient mice that can adapt to the cold have increased oxygen consumption and show increased oxidation of both fat and glucose as indicated from serum metabolite levels and liver glycogen content. Enhanced energy metabolism in inguinal fat was also indicated by increased oxygen consumption and fat oxidation in tissue suspensions and increased AMP kinase activity in dissected tissues. Analysis of gene expression in skeletal muscle showed surprisingly little change between cold-adapted Ucp1+/+ and Ucp1-/- mice, whereas in inguinal fat a robust induction occurred for type 2 deiodinase, sarcoendoplasmic reticulum Ca2+-ATPase, mitochondrial glycerol 3-phosphate dehydrogenase, PGC1alpha, CoxII, and mitochondrial DNA content. Western blot analysis showed an induction of total phospholamban and its phosphorylated form in inguinal fat and other white fat depots, but no induction was apparent in muscle. We conclude that alternative thermogenic mechanisms, based in part upon the enhanced capacity for ion and substrate cycling associated with brown adipocytes in white fat depots, are induced in UCP1-deficient mice by gradual cold adaptation.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA.
authors.forename: Jozef
authors.initials: J
authors.lastname: Ukropec
authors.forename: Rea P
authors.initials: RP
authors.lastname: Anunciado
authors.forename: Yann
authors.initials: Y
authors.lastname: Ravussin
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hulver
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Kozak
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003080:Cold Temperature; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006358:Hot Temperature; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000502:physiology*; D010101:Oxygen Consumption; D013696:Temperature; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000251:Adenosine Triphosphatases