Thermogenic activity of UCP1 in human white fat-derived beige adipocytes.
Heat-producing beige/brite (brown-in-white) adipocytes in white adipose tissue have the potential to suppress metabolic disease in mice and hold great promise for the treatment of obesity and type 2 diabetes in humans. Here, we demonstrate that human adipose-derived stromal/progenitor cells (hASCs) from subcutaneous white adipose tissue can be efficiently converted into beige adipocytes. Upon pharmacological activation of peroxisome proliferator-activated receptor-γ, hASC-derived adipocytes activated beige fat-selective genes and a brown/beige fat-selective electron transport chain gene program. Importantly, hASC-derived beige fat cells displayed the bioenergetic characteristics of genuine brown fat cells, including a capacity for increased respiratory uncoupling in response to β-adrenergic agonists. Furthermore, knock-down experiments reveal that the thermogenic capacity of human beige fat cells was entirely dependent on the presence of Uncoupling protein 1. In summary, this study reveals that hASCs can be readily differentiated into beige adipocytes that, upon activation, undergo uncoupling protein 1-dependent thermogenesis.
Department of Bioscience (S.B., S.H., S.W., E.K.C., X.-R.P..), iMed Cardiovascular and Metabolic Diseases, AstraZeneca, Mölndal, SE-43183 Sweden; Institute for Diabetes, Obesity, and Metabolism (L.H., P.S.), Department Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania 19104; Sahlgrenska Center for Cardiovascular and Metabolic Research (P.-A.S.), Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, SE-41345 Sweden; Department of Translational Science (R.A.M.), iMed Cardiovascular and Metabolic Diseases, AstraZeneca, Mölndal, SE-43183 Sweden; and iPSC/Primary Cell/Stem Cell and Assay Development (A.F.), Discovery Sciences, AstraZeneca, Mölndal, SE-43183 Sweden.
Stefano
S
Bartesaghi
Stefan
S
Hallen
Li
L
Huang
Per-Arne
PA
Svensson
Remi A
RA
Momo
Simonetta
S
Wallin
Eva K
EK
Carlsson
Anna
A
Forslöw
Patrick
P
Seale
Xiao-Rong
XR
Peng
D052437:Adipocytes, Brown / Q000166:cytology*; D052438:Adipocytes, White / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004579:Electron Transport / Q000235:genetics / Q000502:physiology; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D022722:Thermogenesis / Q000502:physiology*; D000071256:Uncoupling Protein 1
D045222:Electron Transport Chain Complex Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D010100:Oxygen