Human Multipotent Adipose-derived Stem Cells Differentiate into Functional Brown Adipocytes.
Résumé
In contrast to the earlier contention, adult humans have been recently shown to possess active brown adipose tissue (BAT) 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 which exhibit the key properties of human white adipocytes, i.e. UCP2 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 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.