title: Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.
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.
authors.affiliation: Wenner-Gren Institute, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. J.Timmons@hw.ac.uk
authors.forename: James A
authors.initials: JA
authors.lastname: Timmons
authors.forename: Kristian
authors.initials: K
authors.lastname: Wennmalm
authors.forename: Ola
authors.initials: O
authors.lastname: Larsson
authors.forename: Tomas B
authors.initials: TB
authors.lastname: Walden
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.forename: Natasa
authors.initials: N
authors.lastname: Petrovic
authors.forename: D Lee
authors.initials: DL
authors.lastname: Hamilton
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Gimeno
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation; D020868:Gene Silencing; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D025341:Principal Component Analysis; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008055:Lipids; D010100:Oxygen; D056564:Sirtuin 1; D037761:Sirtuins; C112923:Tcf21 protein, mouse; C470545:Sirt1 protein, mouse