title: Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver.
abstract: Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production.
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Shore
authors.forename: Angeliki
authors.initials: A
authors.lastname: Karamitri
authors.forename: Paul
authors.initials: P
authors.lastname: Kemp
authors.forename: John R
authors.initials: JR
authors.lastname: Speakman
authors.forename: Neil S
authors.initials: NS
authors.lastname: Graham
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lomax
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D005260:Female; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D013997:Time Factors
references.citation: Proc Nutr Soc. 1992 Aug;51(2):165-72
references.pmid: 1438324
references.citation: J Clin Invest. 2000 Feb;105(3):271-8
references.pmid: 10675352
references.citation: Biochim Biophys Acta. 2000 Apr 21;1457(3):263-72
references.pmid: 10773170
references.citation: J Biol Chem. 2009 Jul 31;284(31):20738-52
references.pmid: 19491401
references.citation: Diabetologia. 2010 Jun;53(6):1164-73
references.pmid: 20238096
references.citation: Izv Akad Nauk Ser Biol. 1997 May-Jun;(3):266-73
references.pmid: 9303752
references.citation: Physiol Rev. 2004 Jan;84(1):277-359
references.pmid: 14715917
references.citation: Biochim Biophys Acta. 2008 Jan;1777(1):104-12
references.pmid: 18036333
references.citation: Genes Dev. 1998 Oct 15;12(20):3168-81
references.pmid: 9784492
references.citation: J Exp Biol. 2011 Jan 15;214(Pt 2):242-53
references.pmid: 21177944
references.citation: J Biol Chem. 2007 Aug 24;282(34):24660-9
references.pmid: 17584738
references.citation: Appl Biochem Biotechnol. 2011 Sep;165(2):538-47
references.pmid: 21556901
references.citation: J Biol Chem. 2000 May 26;275(21):16251-7
references.pmid: 10748195
references.citation: J Clin Invest. 2000 Mar;105(5):615-23
references.pmid: 10712433
references.citation: Mar Genomics. 2010 Mar;3(1):35-44
references.pmid: 21798195
references.citation: Mol Genet Metab. 2003 Sep-Oct;80(1-2):255-61
references.pmid: 14567975
references.citation: Biol Pharm Bull. 2008 May;31(5):775-84
references.pmid: 18451493
references.citation: Nature. 2000 Feb 24;403(6772):850; discussion 850-1
references.pmid: 10706272
references.citation: Biochem Pharmacol. 2004 Feb 1;67(3):555-64
references.pmid: 15037207
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):207-10
references.pmid: 11752295
references.citation: Can J Biochem. 1968 Oct;46(10):1205-13
references.pmid: 4301215
references.citation: Am J Physiol. 1990 Nov;259(5 Pt 2):R1043-9
references.pmid: 2240264
references.citation: Stomatologiia (Mosk). 1998;77(4):37-41
references.pmid: 9752737
references.citation: J Biol Chem. 1997 Nov 28;272(48):30583-8
references.pmid: 9374555
references.citation: Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E19-31
references.pmid: 21828341
references.citation: Aviakosm Ekolog Med. 2000;34(1):35-8
references.pmid: 10732193
references.citation: J Biol Chem. 1997 Nov 28;272(48):30546-51
references.pmid: 9374549
references.citation: Am J Physiol Endocrinol Metab. 2012 Oct 1;303(7):E908-16
references.pmid: 22850683
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R995-R1010
references.pmid: 21734021
references.citation: Mol Cell Biol. 2008 Jun;28(12):3917-31
references.pmid: 18426912
references.citation: Diabetes. 1998 Apr;47(4):507-14
references.pmid: 9568680
references.citation: FEBS Lett. 1995 Apr 17;363(1-2):41-5
references.pmid: 7729550
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14623-8
references.pmid: 10588755
references.citation: J Clin Endocrinol Metab. 1989 Jan;68(1):168-72
references.pmid: 2491858
references.citation: Physiol Rev. 2006 Apr;86(2):435-64
references.pmid: 16601266
references.citation: J Biol Chem. 2000 Mar 24;275(12):8456-60
references.pmid: 10722680
references.citation: Biotechnol Lett. 2011 Feb;33(2):237-42
references.pmid: 20972819