Human Multipotent Adipose-Derived Stem Cells Differentiate into Functional Brown Adipocytes§

Authors


  • Author contributions: C.E.: carried out most of the experiments, data analysis and interpretation, collection and assembly of data; C.C., O.C.: performed gene expression analyses, data analysis and interpretation; M.C., L.P., L.C.: performed oxygen consumption and uncoupled respiration experiments, data analysis and interpretation; R.K.P., K.K., performed gene expression analyses and took part in revising the manuscript; J.G., A.B.: performed gene expression analyses, data analysis and interpretation; C.D.: data analysis and interpretation, financial support; G.A.: conception and design, data analysis and interpretation, manuscript writing; E.A.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS August 20, 2009.

Abstract

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 β-agonists and atrial natriuretic peptide, and release of adiponectin and leptin. Herein, we show that, upon chronic exposure to a specific PPARγ but not to a PPARβ/δ or a PPARα 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 β-AR agonists, including β3-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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