title: Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment.
abstract: Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and palmitoleate. Mice with a targeted disruption of the SCD1 isoform (SCD1-/-) exhibit reduced adiposity and increased energy expenditure. To address whether the energy expenditure is attributable to increased thermogenesis, we investigated the effect of SCD1 deficiency on basal and cold-induced thermogenesis. SCD1-/- mice have increased expression of uncoupling proteins in brown adipose tissue (BAT) relative to controls. The beta3-adrenergic receptor (beta3-AR) expression was increased and the phosphorylation of cAMP response element binding protein and the protein level of peroxisome proliferator-activated receptor-gamma coactivator-1alpha were increased in the SCD1-/- mice. Both lipolysis and fatty acid oxidation were increased in the SCD1-/- mice. When exposed to 4 degrees C, SCD1-/- mice showed hypothermia, hypoglycemia, and depleted liver glycogen. High levels of dietary oleate partially compensated for the hypothermia and rescued plasma glucose and liver glycogen. These results suggest that SCD1 deficiency stimulates basal thermogenesis through the upregulation of the beta3-AR-mediated pathway and a subsequent increase in lipolysis and fatty acid oxidation in BAT. The hypothermia and hypoglycemia in cold-exposed SCD1-/- mice and the compensatory recovery by oleate indicate an important role of SCD1 gene expression in thermoregulation.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dobrzyn
authors.forename: Pawel
authors.initials: P
authors.lastname: Dobrzyn
authors.forename: Shaikh Mizanoor
authors.initials: SM
authors.lastname: Rahman
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyazaki
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001831:Body Temperature; D001833:Body Temperature Regulation / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003080:Cold Temperature; D005227:Fatty Acids / Q000378:metabolism; D007035:Hypothermia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D007473:Ion Channels; D008066:Lipolysis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology*; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D005227:Fatty Acids; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; D000071256:Uncoupling Protein 1; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase