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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 11; pp. 4401 - 4406
• Main Authors: Timmons, James A, Wennmalm, Kristian, Larsson, Ola, Walden, Tomas B, Lassmann, Timo, Petrovic, Natasa, Hamilton, D. Lee, Gimeno, Ruth E, Wahlestedt, Claes, Baar, Keith, Nedergaard, Jan, Cannon, Barbara
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13.03.2007; National Acad Sciences
• Subjects: Adipocytes; Adipocytes - cytology; Adipose Tissue, Brown - cytology; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological Sciences; Brown adipocytes; Cell Differentiation; Cell Lineage; Cell lines; Cells; Cultured cells; Datasets; Gene expression; Gene Expression Regulation; Gene Silencing; Genes; Genotype & phenotype; Lipids - chemistry; Male; Medicin och hälsovetenskap; Mice; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Musculoskeletal system; Myoblasts; Obesity; Oxygen - metabolism; Principal Component Analysis; Signatures; Sirtuin 1; Sirtuins - metabolism; Skeletal muscle; White adipocytes; Muscle; Skeletal/cytology/metabolism; Adipose Tissue; Brown/cytology
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0610615104

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.