TY - JOUR

T1 - Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes

AU - Elabd, Christian

AU - Chiellini, Chiara

AU - Carmona, Mamen

AU - Galitzky, Jean

AU - Cochet, Olivia

AU - Petersen, Rasmus Kofoed

AU - Pénicaud, Luc

AU - Kristiansen, Karsten

AU - Bouloumié, Anne

AU - Casteilla, Louis

AU - Dani, Christian

AU - Ailhaud, Gérard

AU - Amri, Ez-Zoubir

N1 - Keywords: Adipocytes, Brown; Adipose Tissue, White; Blotting, Western; Cell Differentiation; Cell Line; Cell Respiration; Cells, Cultured; Child, Preschool; Humans; Ion Channels; Male; Mitochondrial Proteins; Multipotent Stem Cells; Oxygen Consumption; Receptors, Adrenergic, beta-3; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; Thiazolidinediones

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1002/stem.200

DO - 10.1002/stem.200

M3 - Journal article

C2 - 19697348

VL - 27

SP - 2753

EP - 2760

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 11

ER -