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Karbiener, M.* ; Glantschnig, C. ; Pisani, D.F.* ; Laurencikiene, J.* ; Dahlman, I.* ; Herzig, S. ; Amri, E.Z.* ; Scheideler, M.

Mesoderm Specific Transcript (MEST) is a negative regulator of human adipocyte differentiation.

Int. J. Obes. 39, 1733-1741 (2015)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BackgroundA growing body of evidence suggests that many downstream pathologies of obesity are amplified or even initiated by molecular changes within 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.ObjectivesThis study analysed WAT samples and employed a cell model of adipogenesis to characterise MEST expression and function in human.Methods and ResultsMEST mRNA and protein levels increased during adipocyte differentiation of human Multipotent Adipose-Derived Stem (hMADS) cells. Further, obese individuals displayed significantly higher MEST levels in WAT compared to 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 (PPAR) signaling, 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 inducer of adipogenesis. Accordingly, phosphorylation of the pro-adipogenic transcription factors cAMP response element-binding protein (CREB) and activating transcription factor 1 (ATF1) were highly increased upon MEST knockdown.ConclusionsWhile 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, particularly obesity-associated diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0307-0565
e-ISSN 1476-5497
Zeitschrift International Journal of Obesity
Quellenangaben Band: 39, Heft: 12, Seiten: 1733-1741 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)