Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages
Open accessAbstract
Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue.
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Emerging evidence suggests that brown adipocytes located in different anatomical locations may arise from different developmental origins.
“Emerging evidence suggests that brown adipocytes located in different anatomical locations may arise from different developmental origins.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [91]
Cultured brown fat precursors appear to possess a myogenic signature, which includes myf5.
“In support of this notion, cultured brown fat precursors appear to possess a myogenic signature, which includes myf5 91.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [91]
The genetic program leading to brown adipose tissue development, and potentially to the high abundance of mitochondria, is initiated by the zinc-finger protein PRDM16.
“The genetic program leading to brown adipose tissue development, and potentially to the high abundance of mitochondria, is initiated by the zinc-finger protein PRDM16 (202)(203)(204).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [204]
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- Authors
- Timmons, J. A., Wennmalm, K., Larsson, O., Walden, T. B., Lassmann, T., Petrovic, N., Hamilton, D. L., Gimeno, R. E., Wahlestedt, C., Baar, K., Nedergaard, J., & Cannon, B.
- Affiliations
- Stockholm University (SE)
- Karolinska Institutet (SE)
- *Wenner–Gren Institute, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden;
- University of Dundee (GB)
- Pfizer (United States) (US)
- Scripps Research Institute (US)
- Corresponding author
- Timmons, James A.
- Cannon, Barbara
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-03-13
- Volume
- 104
- Issue
- 11
- Pages
- 4401-4406
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1810328
- OpenAlex
- W1968963111
- Cited by
- 732
- References
- 51
- Citations by year
- 2026: 10 · 2025: 27 · 2024: 19 · 2023: 24 · 2022: 28 · 2021: 39 · 2020: 31 · 2019: 33 · 2018: 43 · 2017: 48 · 2016: 46 · 2015: 59 · 2014: 50 · 2013: 62 · 2012: 51
- FWCI
- 25.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Stirling Online Research Repository (University of Stirling) (submittedVersion, public-domain)
- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- brown adipocytes, white adipocytes, brown adipogenesis, preadipocytes, SIRT1, TCF21, myogenesis, obesity, lipid degradation, transcription factors
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Differentiation, Gene Expression Regulation, Lipids, Male, Oxygen, Adipocytes, Muscle, Skeletal, Cell Lineage, Gene Silencing, Principal Component Analysis, Sirtuins, Mice, Basic Helix-Loop-Helix Proteins, Sirtuin 1
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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