title: Mesoderm-specific transcript (MEST) is a negative regulator of human adipocyte differentiation.
abstract: BACKGROUND
  A growing body of evidence suggests that many downstream pathologies of obesity are amplified or even initiated by molecular changes within the white adipose tissue (WAT). Such changes are the result of an excessive expansion of individual white adipocytes and could potentially be ameliorated via an increase in de novo adipocyte recruitment (adipogenesis). Mesoderm-specific transcript (MEST) is a protein with a putative yet unidentified enzymatic function and has previously been shown to correlate with adiposity and adipocyte size in mouse.
  
  
  OBJECTIVE
  This study analysed WAT samples and employed a cell model of adipogenesis to characterise MEST expression and function in human.
  
  
  RESULTS
  MEST mRNA and protein levels increased during adipocyte differentiation of human multipotent adipose-derived stem cells. Further, obese individuals displayed significantly higher MEST levels in WAT compared with normal-weight subjects, and MEST was significantly correlated with adipocyte volume. In striking contrast to previous mouse studies, knockdown of MEST enhanced human adipocyte differentiation, most likely via a significant promotion of peroxisome proliferator-activated receptor signalling, glycolysis and fatty acid biosynthesis pathways at early stages. Correspondingly, overexpression of MEST impaired adipogenesis. We further found that silencing of MEST fully substitutes for the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) as an inducer of adipogenesis. Accordingly, phosphorylation of the pro-adipogenic transcription factors cyclic AMP responsive element binding protein (CREB) and activating transcription factor 1 (ATF1) were highly increased on MEST knockdown.
  
  
  CONCLUSIONS
  Although we found a similar association between MEST and adiposity as previously described for mouse, our functional analyses suggest that MEST acts as an inhibitor of human adipogenesis, contrary to previous murine studies. We have further established a novel link between MEST and CREB/ATF1 that could be of general relevance in regulation of metabolism, in particular obesity-associated diseases.
authors.affiliation: Department of Phoniatrics, ENT University Hospital, Medical University Graz, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Karbiener
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Glantschnig
authors.affiliation: Université Nice Sophia Antipolis, iBV, UMR, Nice, France.|CNRS, iBV, UMR, Nice, France.|Inserm, iBV, Nice, France.
authors.forename: D F
authors.initials: DF
authors.lastname: Pisani
authors.affiliation: Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Laurencikiene
authors.affiliation: Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Herzig
authors.affiliation: Université Nice Sophia Antipolis, iBV, UMR, Nice, France.|CNRS, iBV, UMR, Nice, France.|Inserm, iBV, Nice, France.
authors.forename: E-Z
authors.initials: EZ
authors.lastname: Amri
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Scheideler
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D052436:Adipose Tissue, White / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D011506:Proteins; D012333:RNA, Messenger; C103637:mesoderm specific transcript protein