title: Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism.
abstract: We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression during cold exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are increased; and 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4. In summary, our results demonstrate extensive and diverse gene expression changes related to glucose handling in activated BAT.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;
authors.forename: Rachita
authors.initials: R
authors.lastname: Yadav
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Astrid L
authors.initials: AL
authors.lastname: Basse
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Sidsel
authors.initials: S
authors.lastname: Petersen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Si B
authors.initials: SB
authors.lastname: Sonne
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;
authors.forename: Simon
authors.initials: S
authors.lastname: Rasmussen
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China;
authors.forename: Qianhua
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China;
authors.forename: Zhike
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China; Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China; Department of Medicine, University of Hong Kong, Hong Kong;
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark; Université Paris Diderot, Inserm UMR-S973, Paris, France; and.
authors.forename: Karine
authors.initials: K
authors.lastname: Audouze
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;
authors.forename: Ramneek
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Nordnes, Bergen, Norway.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China;
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark; jacob.hansen@bio.ku.dk.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Hansen
mesh_terms: D000064:Acclimatization / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000235:genetics; D050260:Carbohydrate Metabolism / Q000235:genetics*; D002478:Cells, Cultured; D003080:Cold Temperature; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013312:Stress, Physiological / Q000235:genetics; D059467:Transcriptome
chemical_list: D005947:Glucose
keywords: glycolysis; pyruvate dehydrogenase; thermogenesis