Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes.
In contrast to the earlier contention, adult humans have been shown recently to possess active brown adipose tissue with a potential of being of metabolic significance. Up to now, brown fat precursor cells have not been available for human studies. We have shown previously that human multipotent adipose-derived stem (hMADS) cells exhibit a normal karyotype and high self-renewal ability; they are known to differentiate into cells that exhibit the key properties of human white adipocytes, that is, uncoupling protein two expression, insulin-stimulated glucose uptake, lipolysis in response to beta-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARgamma but not to a PPARbeta/delta or a PPARalpha agonist, hMADS cell-derived white adipocytes are able to switch to a brown phenotype by expressing both uncoupling protein one (UCP1) and CIDEA mRNA. This switch is accompanied by an increase in oxygen consumption and uncoupling. The expression of UCP1 protein is associated to stimulation of respiration by beta-AR agonists, including beta3-AR agonist. Thus, hMADS cells represent an invaluable cell model to screen for drugs stimulating the formation and/or the uncoupling capacity of human brown adipocytes that could help to dissipate excess caloric intake of individuals.
Elabd
Christian
C
IBDC, Université de Nice Sophia-Antipolis, CNRS, 06 107 Nice cedex 2, France.
Chiellini
Chiara
C
Carmona
Mamen
M
Galitzky
Jean
J
Cochet
Olivia
O
Petersen
Rasmus
R
Pénicaud
Luc
L
Kristiansen
Karsten
K
Bouloumié
Anne
A
Casteilla
Louis
L
Dani
Christian
C
Ailhaud
Gérard
G
Amri
Ez-Zoubir
EZ
D052437:Adipocytes, Brown / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology*; D000728:Androgens; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D000071256:Uncoupling Protein 1
D000728:Androgens; D007473:Ion Channels; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; D045162:Thiazolidinediones; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D000077154:Rosiglitazone