Endocrine Abstracts

Obesity-associated inflammation is a major contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the mechanisms underlying the progression of T2DM are yet to be fully elucidated. The adipokine, resistin, has recently been implicated as a pro-inflammatory cytokine in obesity-related T2DM. Therefore, the aim of this study was to characterise the role of resistin in the innate immune inflammatory pathway within isolated human abdominal subcutaneous (Abd Sc) adipocytes. In particular, we examined the acute in vitro effects of human recombinant (h-r) resistin on different components of the NF-κB and JNK signalling pathways. For this study, isolated human Abd Sc adipocytes were treated for 14 hours with increasing concentrations of h-r resistin (10–50 ng). Innate immunity intracellular protein expression, in response to h-r resistin, was examined by Western blotting. Results demonstrated that h-r resistin upregulated components of the NF-κB pathway. Protein expression of MyD88 (n=4, P<0.01), IκBα (n=4, P<0.001) and NF-κB (n=4, P<0.05) was increased in response to h-r resistin. Similarly, h-r resistin upregulated central mediators of the insulin signalling pathway; phosphospecific JNK1 and JNK2 (JNK-1: n=6, P<0.05; JNK-2: n=6, P<0.001) were both increased in response to h-r resistin treatment. Furthermore, when examining the IKK complex, the central activator of IκBα in the NF-κB pathway, IKKα was upregulated in response to h-r resistin (n=6, P<0.01). Taken together, these findings suggest that resistin could participate in more than one mechanism for the stimulation of pro-inflammatory cytokine release in human Abd Sc adipocytes; potentially via the integration of NF-κB and JNK intracellular signalling pathways. This study further emphasises crosstalk between insulin signalling and inflammatory pathways, in addition to confirming adipose tissue as an important site for the progression of sub-clinical inflammation and insulin resistance.