Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages

James A. Timmons, Kristian Wennmalm, Ola Larsson, Tomas B. Walden, Timo Lassmann, Natasa Petrovic, D. Lee Hamilton, Ruth E. Gimeno, Claes Wahlestedt, Keith Baar, Jan Nedergaard, Barbara Cannon

Research output: Contribution to journalArticle

462 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4401-4406
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number11
DOIs
StatePublished - Mar 13 2007
Externally publishedYes

Keywords

  • Differentiation
  • Microarray
  • Myocyte
  • Principal component analysis
  • Transcriptome

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages'. Together they form a unique fingerprint.

  • Cite this

    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. (2007). Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proceedings of the National Academy of Sciences of the United States of America, 104(11), 4401-4406. https://doi.org/10.1073/pnas.0610615104