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Chronic Perixosome Proliferator-activated Receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classical brown adipocytes.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
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2010 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 285, no 10, 7153-7164 p.Article in journal (Refereed) Published
Abstract [en]

The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classical white adipose tissue depots under certain physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the PPARgamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis in these cells but also a norepinephrine-augmentable UCP1 gene expression in a significant subset of the cells, providing these cells with a genuine thermogenic capacity. However, although functional thermogenic genes are expressed, the cells are devoid of transcripts for the novel transcription factors now associated with classical brown adipocytes (Zic1, Lhx8, Meox2 and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white-fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells are not proliferating classical brown adipocytes (adipomyocytes) and these cells therefore constitute a subset of adipocytes (''brite'' adipocytes) with a developmental origin and molecular characteristics distinguishing them as a separate class of cells.

Place, publisher, year, edition, pages
2010. Vol. 285, no 10, 7153-7164 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-33830DOI: 10.1074/jbc.M109.053942ISI: 000275415600029PubMedID: 20028987OAI: oai:DiVA.org:su-33830DiVA: diva2:283719
Available from: 2009-12-30 Created: 2009-12-30 Last updated: 2017-12-12Bibliographically 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.
Keyword
adipocyte, UCP1, brite, brown, white, Hox Zic, miRNA
National Category
Physiology
Research subject
Physiology
Identifiers
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)
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Note
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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