hamilton-myogenicgeneexpression-2007.pdf (1.33 MB)
Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages
journal contribution
posted on 2007-03-13, 00:00 authored by James A Timmons, Kristian Wennmalm, Ola Larsson, Tomas B Walden, Timo Lassmann, Natasa Petrovic, Lee HamiltonLee Hamilton, Ruth E Gimeno, Claes Wahlestedt, Keith Baar, Jan Nedergaard, Barbara CannonAttainment 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.
History
Journal
Proceedings of the national academy of sciencesVolume
104Issue
11Pagination
4401 - 4406Publisher
National Academy of SciencesLocation
Washington, D. C.Publisher DOI
Link to full text
ISSN
0027-8424Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2007, The National Academy of Sciences of the USAUsage metrics
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No categories selectedKeywords
AdipocytesAdipose Tissue, BrownAnimalsBasic Helix-Loop-Helix Transcription FactorsCell DifferentiationCell LineageGene Expression RegulationGene SilencingLipidsMaleMiceMuscle, SkeletalOxygenPrincipal Component AnalysisSirtuin 1SirtuinsScience & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsmicroarraymyocytedifferentiationtranscriptomeLOOP-HELIX TRANSCRIPTIONSKELETAL-MUSCLEADIPOSE-TISSUEPPAR-GAMMAMITOCHONDRIAL ACTIVITYMODULATIONPROTEINNECDINROSIGLITAZONE
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