Nf Kappa B As A Potent Regulator Of Inflammation In Human Adipose Tissue, Influenced By Depot, Adiposity, T2dm Status, And Tnf Alpha

Objective: Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk.Design and Methods: This study therefore addressed the influence of NF kappa B and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNF alpha in vitro, using molecular biology techniques.Results: Our data showed NF kappa B activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NF kappa B (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNF alpha treated AbdSc adipocytes increased NF kappa B activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NF kappa B as a modulator of TNF alpha secretion.Conclusions: These studies suggest distinct changes in NF kappa B and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNF alpha leading to activation of NF kappa B. Consequently NF kappa B appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NF kappa B as a potential key target for therapeutic intervention.