A reservoir of brown adipocyte progenitors in human skeletal muscle.
Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-gamma (PPARgamma) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPARgamma agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.
Crisan
Mihaela
M
Stem Cell Research Center, Children's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Casteilla
Louis
L
Lehr
Lorenz
L
Carmona
Mamen
M
Paoloni-Giacobino
Ariane
A
Yap
Solomon
S
Sun
Bin
B
Léger
Bertrand
B
Logar
Alison
A
Pénicaud
Luc
L
Schrauwen
Patrick
P
Cameron-Smith
David
D
Russell
Aaron Paul
AP
Péault
Bruno
B
Giacobino
Jean-Paul
JP
D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000071256:Uncoupling Protein 1
D018952:Antigens, CD34; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1