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

Fas (CD95) expression in adipocytes contributes to diet-induced obesity.

Obesity, DOI: 10.1002/oby.24092 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
OBJECTIVE: Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity. METHODS: Adipocyte-specific Fas knockout (FasΔadipo) and control littermate (FasF/F) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, FAS expression in WAT was correlated to UCP1 and percentage of body fat in human individuals. RESULTS: HFD-fed FasΔadipo mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole-body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol-induced UCP1 protein levels. In support of these findings in rodents, FAS expression in WAT correlated negatively with UCP1 but positively with adiposity in human individuals. CONCLUSIONS: Fas activation in adipocytes contributes to HFD-associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adipose-tissue; Pitfalls; Brown; Cells
ISSN (print) / ISBN 1930-7381
e-ISSN 1930-739X
Zeitschrift Obesity
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen University of Birmingham
Maastricht University