Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
The ligand-activated transcription factor peroxisome proliferator-activated receptor-[alpha] (PPAR[alpha]) participates in the regulation of cellular inflammation. More recent studies indicated that sirtuin1 (SIRT1), a NAD+ -dependent deacetylase, regulates the inflammatory response in adipocytes. However, whether the role of PPAR[alpha] in inflammation is mediated by SIRT1 remains unclear. In this study, we aimed to determine the effect of PPAR[alpha] agonist fenofibrate on the expressions of SIRT1 and pro-inflammatory cytokine CD40 and underlying mechanisms in 3T3-L1 adipocytes. We found that fenofibrate inhibited CD40 expression and up-regulated SIRT1 expression in tumor necrosis factor-[alpha] (TNF-[alpha])-stimulated adipocytes, and these effects of fenofibrate were reversed by PPAR[alpha] antagonist GW6471. Moreover, SIRT1 inhibitors sirtinol/nicotinamide (NAM) or knockdown of SIRT1 could attenuate the effect of fenofibrate on TNF-[alpha]-induced CD40 expression in adipocytes. Importantly, NF-[kappa]B inhibitor pyrrolidine dithiocarbamate (PDTC) augmented the effect of fenofibrate on CD40 expression in adipocytes. Further study found that fenofibrate decreased the expression of acetylated-NF-[kappa]B p65 (Ac-NF-[kappa]B p65) in TNF-[alpha]-stimulated adipocytes, and the effect of fenofibrate was abolished by SIRT1 inhibition. In addition, fenofibrate up-regulated SIRT1 expression through AMPK in TNF-[alpha]-stimulated adipocytes. Taken together, these findings indicate that PPAR[alpha] agonist fenofibrate inhibits TNF-[alpha]-induced CD40 expression in 3T3-L1 adipocytes via the SIRT1-dependent signaling pathway. [PUBLICATION ABSTRACT]