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Wueest, S.* ; Scaffidi, C.* ; van Krieken, P.P.* ; Konrad, N.K.* ; Koch, C.* ; Lempesis, I.G.* ; Fullin, J.* ; Manolopoulos, K.N.* ; Böttcher, S.* ; Goossens, G.H.* ; Blüher, M. ; Konrad, D.*

Expression of p53 in human adipose tissue correlates positively with FAS and BMI.

Int. J. Obes., DOI: 10.1038/s41366-024-01691-4 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Activation of Fas (CD95) in adipocytes inhibits browning and may contribute to body weight gain in mice. Moreover, Fas expression in white adipose tissue (WAT) correlates positively with body mass index (BMI) in humans. However, molecular pathways involved in the inhibitory effect of Fas on energy metabolism remain incompletely understood. Herein, we report that protein levels of the tumor suppressor p53 were reduced in primary white adipocytes of adipocyte-specific Fas-knockout mice. Moreover, Fas ligand (FasL) treatment increased p53 concentrations in cultured adipocytes and decreased mitochondrial oxygen consumption in control but not in p53-depleted cells, indicating that Fas activation reduces energy expenditure in a p53-dependent manner. In line, in differentiated human mesenchymal stem cells and WAT derived from different anatomical depots, FAS expression was positively associated with p53. Furthermore, p53 expression in human subcutaneous and visceral WAT correlated positively with BMI, whereas its expression in visceral WAT was inversely associated with insulin sensitivity (as assessed by hyperinsulinemic-euglycemic clamp). Taken together, our data suggest that Fas regulates p53 expression in adipocytes, and may thereby affect body weight gain and insulin sensitivity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Insulin-resistance; Inflammation
ISSN (print) / ISBN 0307-0565
e-ISSN 1476-5497
Journal International Journal of Obesity
Publisher Nature Publishing Group
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants University of Zurich
University of Birmingham (UK)
Maastricht University (the Netherlands)
European Foundation
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Swiss National Science Foundation