Gene expression in human brown adipose tissue.
Brown adipose tissue (BAT) has profound effects on body weight and metabolism in rodents. Recent reports show that human adults have significant amounts of BAT. Our aim was to study the gene expression profile of human BAT. Biopsies of adipose tissue with brown-red color and subcutaneous white adipose tissue (WAT) were obtained from 24 patients undergoing surgery in the thyroid region. Intrascapular BAT and epididymal WAT biopsies were obtained from 10 mice. Expression was analyzed by DNA microarray, real-time PCR and immunohistochemistry. Using the expression of the brown adipocyte-specific gene uncoupling protein 1 (UCP1) as a marker, approximately half of the human brown-red adipose tissue biopsies taken in the thyroid region contained BAT, and the presence of cells with brown adipocyte morphology was also verified by histology. Microarray analysis of 9 paired human BAT and WAT samples showed that 17 genes had at least a 4-fold higher expression in BAT compared to WAT and five of them (CKMT1, KCNK3, COBL, HMGCS2, TGM2) were verified using real-time PCR (P<0.05 for all). In addition, immunohistochemistry showed that the UCP1, KCNK3 and CKMT1 proteins are expressed in brown adipocytes. Except for UCP1 and KCNK3, the genes overexpressed in human BAT were not overexpressed in mouse BAT compared to mouse WAT. Our analysis identified genes that are differentially expressed in human BAT compared to WAT. The results also show that there are species-specific differences in BAT gene expression and this emphasizes the need for further molecular characterization of human BAT to clarify the mechanisms involved in regulated heat production in humans.
Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. per-arne.svensson@gu.se
Per-Arne
PA
Svensson
Margareta
M
Jernås
Kajsa
K
Sjöholm
Jenny M
JM
Hoffmann
Bengt E
BE
Nilsson
Magnus
M
Hansson
Lena M S
LM
Carlsson
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D000071256:Uncoupling Protein 1; D055815:Young Adult
D007473:Ion Channels; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C420132:potassium channel subfamily K member 3; C519581:CKMT1A protein, human; D003402:Creatine Kinase