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 R Wahlestedt, Keith Baar, Jan Nedergaard, Barbara Cannon

Research output: Contribution to journalArticle

447 Citations (Scopus)

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
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

Fingerprint

White Adipocytes
Brown Adipocytes
Cell Lineage
Transcriptome
Muscle Cells
Skeletal Muscle
Obesity
Developmental Genes
Phenotype
Adipogenesis
White Adipose Tissue
Muscle Development
Microarray Analysis
Cytoplasmic and Nuclear Receptors
Energy Metabolism
Mitochondria
Transcription Factors
Lipids
Muscles

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. / Timmons, James A.; Wennmalm, Kristian; Larsson, Ola; Walden, Tomas B.; Lassmann, Timo; Petrovic, Natasa; Hamilton, D. Lee; Gimeno, Ruth E.; Wahlestedt, Claes R; Baar, Keith; Nedergaard, Jan; Cannon, Barbara.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 11, 13.03.2007, p. 4401-4406.

Research output: Contribution to journalArticle

Timmons, JA, Wennmalm, K, Larsson, O, Walden, TB, Lassmann, T, Petrovic, N, Hamilton, DL, Gimeno, RE, Wahlestedt, CR, 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, vol. 104, no. 11, pp. 4401-4406. https://doi.org/10.1073/pnas.0610615104
Timmons, James A. ; Wennmalm, Kristian ; Larsson, Ola ; Walden, Tomas B. ; Lassmann, Timo ; Petrovic, Natasa ; Hamilton, D. Lee ; Gimeno, Ruth E. ; Wahlestedt, Claes R ; Baar, Keith ; Nedergaard, Jan ; Cannon, Barbara. / Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 11. pp. 4401-4406.
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