Aim/hypothesis: MAP-kinases and IB kinase (IKK) were suggested to link various conditions thought to develop in adipose tissue in obesity (oxidative, endoplasmic reticulum stress, inflammation) with insulin resistance. Yet, whether in obesity these kinases are affected in a fat-depot -differential manner is unknown.

Methods: We assessed the expression and phosphorylation of these kinases in paired omental and abdominal-subcutaneous fat biopsies from 48 severely obese (BMI>32Kg/m²) women.

Results: Protein and mRNAs of p38MAPK, ERK, JNK1 and IKK were increased 1.5-2.5-fold in omental versus subcutaneous fat. The phosphorylated (activated) forms of these kinases were also increased to similar magnitudes as the total expression. However, phosphorylation of IRS1 on Ser312 (equivalent of murine Ser307) was not increased in omental compared to subcutaneous fat. Consistently, fat tissue fragments stimulated with insulin demonstrated that tyrosine phosphorylation and signal transduction to Akt/PKB in omental fat was not inferior to that observable in subcutaneous fat. Comparison to lean women (BMI=23.2±2.9Kg/m²) revealed similar ERK2 and IKK expression and phosphorylation in both fat depots. However, as compared to lean controls, obese women exhibited 480% and 270% higher amount of the phosphorylated forms of p38MAPK and JNK, respectively, in omental, but not in subcutaneous fat, and this expression level correlated with clinical parameters of glycemia and insulin sensitivity.

Conclusions: Increased expression of stress-activated kinases and of IKK and their phosphorylated forms in omental fat occurs in obesity potentially contributing to differential contributions of omental and subcutaneous fat to the pathophysiology of obesity.