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Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2007 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 104, no 11, 4401-4406 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 104, no 11, 4401-4406 p.
Keyword [en]
Adipocytes/*cytology, Adipose Tissue; Brown/*cytology, Animals, Basic Helix-Loop-Helix Transcription Factors/metabolism, Cell Differentiation, Cell Lineage, Gene Expression Regulation, Gene Silencing, Lipids/chemistry, Male, Mice, Muscle; Skeletal/*cytology/metabolism, Oxygen/metabolism, Principal Component Analysis, Sirtuins/metabolism
URN: urn:nbn:se:su:diva-20877DOI: 10.1073/pnas.0610615104ISI: 000244972700030PubMedID: 17360536OAI: diva2:187403
Available from: 2008-01-18 Created: 2008-01-18 Last updated: 2010-04-12Bibliographically approved
In thesis
1. Regulatory Factors that Reveal Three Distinct Adipocytes: The Brown, the White and the Brite
Open this publication in new window or tab >>Regulatory Factors that Reveal Three Distinct Adipocytes: The Brown, the White and the Brite
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adipose tissues have long been considered to derive from a common origin. Even the functionally different brown and white adipose tissues were generalized to share a common origin. Brown adipose tissue is a highly innervated and vascularised tissue containing multilocular and multimitochondrial brown adipocytes. Brown adipose tissue expends energy through sympathetic nervous system-mediated non-shivering thermogenesis, where uncoupling protein 1 (UCP1) is the key player. In contrast, white adipose tissue consists of unilocular white adipocytes with a main role to store energy in the form of the lipid droplet.

We know today that this generalisation is exaggerated since adipocytes can derive from more than one origin and not only be brown or white. We and others have demonstrated that the brown adipocyte has a dermomyotomal origin and derives from the adipomyocyte, the precursor cell that can also become a myocyte, whereas white adipocytes are suggested to derive from pericytes, cells that are embedded within the vascular vessel walls. For a long time there has been evidence that energy-expending adipocytes reside within certain white adipose tissues, based on the fact that cold exposure, by switching on the sympathetic nervous system, leads to levels of UCP1 that are not detectable in mice housed at thermoneutrality. We demonstrated that these cells have a molecular signature that is distinct from brown and white adipocytes. Since these energy-expending cells reside within certain white adipose tissues, we chose to name them brite (brown in white) adipocytes. Moreover, we also identified regulatory factors that were specifically expressed in each adipocyte type, thus, facilitating the possibility to identify the three adipocytes: the brown, the white and the brite.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 89 p.
adipocyte, UCP1, brite, brown, white, Hox Zic, miRNA
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Research subject
urn:nbn:se:su:diva-38362 (URN)978-91-7447-048-2 (ISBN)
Public defence
2010-05-12, sal E306, Arrheniuslaboratorierna, Svante Arrhenius väg 20 C, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript. Available from: 2010-04-20 Created: 2010-04-09 Last updated: 2010-04-22Bibliographically approved

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Walden, Tomas BPetrovic, NatasaNedergaard, JanCannon, Barbara
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