Human Multipotent Adipose-Derived Stem Cells Differentiate into Functional Brown Adipocytes
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. Disclosure of potential conflicts of interest is found at the end of this article.
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It may be possible to increase oxidative capacities in skeletal muscle and white fat by targeting endogenous brown fat progenitors to differentiate in vivo and produce energy-dissipating BAT.
“Recently, brown fat progenitors have been identified in skeletal muscle and white fat of humans 120,121, suggesting that it may be possible to increase oxidative capacities in these tissues by targeting these endogenous precursors to differentiate in vivo, and produce energy-dissipating BAT.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [120]
Brown fat progenitors have been identified in skeletal muscle and white fat of humans.
“Recently, brown fat progenitors have been identified in skeletal muscle and white fat of humans 120,121, suggesting that it may be possible to increase oxidative capacities in these tissues by targeting these endogenous precursors to differentiate in vivo, and produce energy-dissipating BAT.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [120]
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Naringenin Promotes Thermogenic Gene Expression in Human White Adipose Tissue
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Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes.
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Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation
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Self-citationHuman White and Brite Adipogenesis is Supported by MSCA1 and is Impaired by Immune Cells
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Self-citationMetabolic programming of a beige adipocyte phenotype by genistein
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An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes
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Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis
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Self-citationBrown adipose tissue and novel therapeutic approaches to treat metabolic disorders
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Self-citationLet-7i-5p represses brite adipocyte function in mice and humans
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Self-citationCould Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?
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20 Years with SGBS cells - a versatile in vitro model of human adipocyte biology
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Self-citationMesoderm-specific transcript (MEST) is a negative regulator of human adipocyte differentiation
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Self-citationGrape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes
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- Authors
- Elabd, C., Chiellini, C., Carmona, M., Galitzky, J., Cochet, O., Petersen, R., Pénicaud, L., Kristiansen, K., Bouloumié, A., Casteilla, L., Dani, C., Ailhaud, G., & Amri, E.-Z.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- University of Copenhagen (DK)
- IBDC, Université de Nice Sophia-Antipolis, CNRS, Nice, France
- Corresponding author
- Amri, Ez-Zoubir
- ORCID
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08-20
- Volume
- 27
- Issue
- 11
- Pages
- 2753-2760
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W1974058241
- Cited by
- 252
- References
- 66
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 18 · 2019: 21 · 2018: 23 · 2017: 11 · 2016: 19 · 2015: 24 · 2014: 26 · 2013: 21 · 2012: 17
- FWCI
- 9.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- HAL (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Equipe FRM, soutenue par la Fondation pour la Recherche Médicale
- Danish Natural Science Research Council, the NOVO Foundation
- Danish Obesity Research Centre
- The Danish Council for Strategic Research (2101-06-0005)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- human adipose-derived stem cells, brown adipocytes, brown adipose tissue, PPARγ agonists, UCP1, CIDEA, beta3-adrenergic agonists, oxygen consumption, uncoupling, adipose tissue thermogenesis, drug screening model
- MeSH terms
- Uncoupling Protein 1, Rosiglitazone, Androgens, Cell Differentiation, Cell Line, Cells, Cultured, Child, Preschool, Humans, Ion Channels, Male, Oxygen Consumption, Blotting, Western, Cell Respiration, Reverse Transcriptase Polymerase Chain Reaction, Receptors, Adrenergic, beta-3, Mitochondrial Proteins, Multipotent Stem Cells, Thiazolidinediones, Adipose Tissue, White, Adipocytes, Brown
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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