Journal
STEM CELLS
Volume 27, Issue 11, Pages 2753-2760Publisher
WILEY
DOI: 10.1002/stem.200
Keywords
Stem cells; Rosiglitazone; Adipocyte; Differentiation; Uncoupling protein one; Brown adipose tissue; White adipose tissue
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Funding
- Centre National de la Recherche Scientifique
- Equipe FRM, soutenue par la Fondation pour la Recherche Medicale
- Danish Natural Science Research Council
- NOVO Foundation
- Danish Council for Strategic Research [2101-06-0005]
- Fondation pour la Recherche Medicale
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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 PPAR gamma but not to a PPAR beta/delta or a PPAR alpha 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 beta 3-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. STEM CELLS 2009; 27: 2753-2760
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