Abstract
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.