title: Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice.
abstract: We compared maximal cold-induced heat production (HPmax) and cold limits between warm (WA; 27°C), moderate cold (MCA; 18°C), or cold acclimated (CA; 5°C) wild-type and uncoupling-protein 1 knockout (UCP1-KO) mice. In wild-type mice, HPmax was successively increased after MCA and CA, and the cold limit was lowered to -8.3°C and -18.0°C, respectively. UCP1-KO mice also increased HPmax in response to MCA and CA, although to a lesser extent. Direct comparison revealed a maximal cold-induced recruitment of heat production by +473 mW and +227 mW in wild-type and UCP1-KO mice, respectively. The increase in cold tolerance of UCP1-KO mice from -0.9°C in MCA to -10.1°C in CA could not be directly related to changes in HPmax, indicating that UCP1-KO mice used the dissipated heat more efficiently than wild-type mice. As judged from respiratory quotients, acutely cold-challenged UCP1-KO mice showed a delayed transition toward lipid oxidation, and 5-h cold exposure revealed diminished physical activity and less variability in the control of metabolic rate. We conclude that BAT is required for maximal adaptive thermogenesis but also allows metabolic flexibility and a rapid switch toward sustained lipid-fuelled thermogenesis as an acute response to cold. In both CA groups, expression of contractile proteins (myosin heavy-chain isoforms) showed minor training effects in skeletal muscles, while cardiac muscle of UCP1-KO mice had novel expression of beta cardiac isoform. Neither respiration nor basal proton conductance of skeletal muscle mitochondria were different between genotypes. In subcutaneous white adipose tissue of UCP1-KO mice, cold exposure increased cytochrome-c oxidase activity and expression of the cell death-inducing DFFA-like effector A by 3.6-fold and 15-fold, respectively, indicating the recruitment of mitochondria-rich brown adipocyte-like cells. Absence of functional BAT leads to remodeling of white adipose tissue, which may significantly contribute to adaptive thermogenesis during cold acclimation.
authors.affiliation: Dept. of Animal Physiology, Faculty of Biology, Philipps-Universität, Karl-von-Frisch Strasse 8, 35032 Marburg, Germany. meyerc@staff.uni-marburg.de
authors.forename: Carola W
authors.initials: CW
authors.lastname: Meyer
authors.forename: Monja
authors.initials: M
authors.lastname: Willershäuser
authors.forename: Martin
authors.initials: M
authors.lastname: Jastroch
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Rourke
authors.forename: Tobias
authors.initials: T
authors.lastname: Fromme
authors.forename: Rebecca
authors.initials: R
authors.lastname: Oelkrug
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heldmaier
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
mesh_terms: D000064:Acclimatization; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D003080:Cold Temperature; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D007473:Ion Channels / Q000172:deficiency* / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D010084:Oxidation-Reduction; D050151:Subcutaneous Fat / Q000378:metabolism*; D013814:Thermal Conductivity; D022722:Thermogenesis; D013697:Thermosensing; D013997:Time Factors; D000071256:Uncoupling Protein 1
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D003576:Electron Transport Complex IV; D018995:Myosin Heavy Chains
references.citation: Eur J Biochem. 1974 Dec 16;50(1):305-15
references.pmid: 4452361
references.citation: J Mol Cell Cardiol. 2007 Oct;43(4):388-403
references.pmid: 17720186
references.citation: J Comp Physiol B. 2011 Jan;181(1):137-45
references.pmid: 20680295
references.citation: Physiol Biochem Zool. 2003 Nov-Dec;76(6):877-87
references.pmid: 14988803
references.citation: J Biol Chem. 2010 Jul 16;285(29):21961-8
references.pmid: 20466728
references.citation: Cell Metab. 2010 Apr 7;11(4):248-52
references.pmid: 20374955
references.citation: Comp Biochem Physiol A Comp Physiol. 1971 Dec;40(4):1107-8
references.pmid: 4400095
references.citation: J Clin Invest. 1996 Jun 15;97(12):2898-904
references.pmid: 8675704
references.citation: J Exp Zool. 1987 Jun;242(3):263-71
references.pmid: 3612050
references.citation: Biochem Soc Trans. 1995 May;23(2):371-6
references.pmid: 7672401
references.citation: J Comp Physiol B. 1987;157(5):625-33
references.pmid: 3693622
references.citation: Neuroscience. 2009 Dec 1;164(2):849-61
references.pmid: 19679172
references.citation: FASEB J. 2008 Nov;22(11):3919-24
references.pmid: 18687806
references.citation: Biochim Biophys Acta. 1990 Jul 25;1018(2-3):128-33
references.pmid: 2393654
references.citation: Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1230-6
references.pmid: 12954594
references.citation: FEBS Lett. 1984 Feb 13;167(1):10-4
references.pmid: 6698197
references.citation: Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E350-7
references.pmid: 16595854
references.citation: J Appl Physiol (1985). 1993 Nov;75(5):2337-40
references.pmid: 8307894
references.citation: Physiol Rev. 2004 Jan;84(1):277-359
references.pmid: 14715917
references.citation: J Biol Chem. 2006 Oct 20;281(42):31894-908
references.pmid: 16914547
references.citation: Nat Genet. 2003 Sep;35(1):49-56
references.pmid: 12910269
references.citation: J Comp Physiol B. 2001 Nov;171(8):661-8
references.pmid: 11765975
references.citation: J Comp Physiol B. 1992;162(8):696-706
references.pmid: 1494028
references.citation: FASEB J. 2001 Sep;15(11):2048-50
references.pmid: 11511509
references.citation: Am J Physiol Endocrinol Metab. 2000 Oct;279(4):E941-6
references.pmid: 11001779
references.citation: Anal Biochem. 1985 Mar;145(2):406-18
references.pmid: 4014672
references.citation: Pflugers Arch. 2006 Jun;452(3):363-9
references.pmid: 16395600
references.citation: Physiol Genomics. 2008 Jan 17;32(2):161-9
references.pmid: 17971503
references.citation: J Biol Chem. 2008 Oct 10;283(41):27688-27697
references.pmid: 18678870
references.citation: J Lipid Res. 1996 Aug;37(8):1685-95
references.pmid: 8864952
references.citation: J Comp Physiol B. 2003 Jul;173(5):437-42
references.pmid: 12756485
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2008 Jun;150(2):189-95
references.pmid: 17045501
references.citation: Nature. 1997 May 1;387(6628):90-4
references.pmid: 9139827
references.citation: J Clin Invest. 2003 Feb;111(3):399-407
references.pmid: 12569166
references.citation: Experientia Suppl. 1978;32:147-51
references.pmid: 274305
references.citation: PLoS One. 2010 Jun 30;5(6):e11391
references.pmid: 20613988
references.citation: Obes Res. 2004 Sep;12(9):1509-18
references.pmid: 15483216
references.citation: Biochim Biophys Acta. 1994 Dec 30;1188(3):405-16
references.pmid: 7803454
references.citation: Science. 2010 May 28;328(5982):1158-61
references.pmid: 20448152
references.citation: Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):968-80
references.pmid: 20227385