Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 13 P183

1University of Warwick, Unit for Diabetes & Metabolism, CSRI, Coventry, United Kingdom; 2Cellular Pathology Department, Birmingham, United Kingdom.


Central obesity is strongly associated with sub-clinical inflammation, insulin resistance (IR) and type 2 diabetes mellitus (T2DM), but the intracellular mechanisms involved in the pathogenesis of central obesity remain unclear. Recent studies have implicated NFκB and c-jun N terminal kinase (JNK) as central molecules linking insulin action and inflammation in mice. As such we examined (1) the inflammatory intracellular signaling pathways involving NFκB, JNK as a potential adipocytokine activation mechanism leading to inflammation in human abdominal subcutaneous (AbdSc) and omental (Om) adipose tissue (AT); (2) the effects of TNF-α, a known mediator of inflammation in mice, on NFκB and JNK activity in human AbdSc adipocytes. Our data showed that IKKβ and IKKγ protein expression were increased in Om AT compared with AbdSc AT (P<0.01) and similarly IκBα and IκBα-P were also increased in Om (P<0.01). The ratio of active NFκB to total NFκB expression (NFκB ratio) was upregulated in Om AT compared with AbdSc in both lean and obese subjects (P<0.05);. Furthermore, NFκB ratio and IκBα-P expression was also raised in obese Om AT (P<0.05). NFκB activity was increased in a dose dependent manner in AbdSc adipocytes treated with TNF-α (P<0.05). Whilst in the AbdSc depot, phosphospecific active JNK1 was increased 5.8 fold (P<0.01), which was not observed in the Om AT depot. However, no effect was observed on JNK protein expression with(TNF-α treatment or increasing adiposity in both depots. In conclusion, these studies suggest human Om and AbdSc AT depots are regulated by differential expression of the NFκB and JNK inflammatory signalling pathways. NFκB appears to play a more central role in the omental adiposity, whilst JNK appears to be one of the major mediators of inflammation in AbdSc adipose tissue; hence highlighting the different intrinsic nature of these fat depots.

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