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Critical Evaluation of a Journal Article

Introduction to the context of the study

Adipose tissue is linked to induction of insulin resistance, with different fat depots having different impact on health. Indeed, the distribution of body fat appears to be more important than the total amount of fat. Abdominal and, in particular, visceral adipose tissue has been strongly associated with the development of insulin resistance, type 2 diabetes as well as dyslipidaemia, hypertension and cardiovascular disease. Moreover, surgical removal of visceral fat leads to a metabolic improvement in insulin-resistant humans and rodents.

Studies utilizing primary human tissues have obvious limitations of low sample numbers. However, as differences between subcutaneous and visceral adipocytes are retained upon their differentiation in vitro, more detailed molecular and mechanistic analysis could be performed using human cell lines. Experiments using cells cultured in vitro, as well as animal models, could help in dissecting the critical role of p38 MAPK in adipose tissue, for example by using pharmacological inhibitors (eg. PD169316), knock-down strategies (siRNAs or shRNAs), or a knock-out approach. In particular, the role of p38 MAPK in insulin-mediated glucose uptake by adipose tissue remains controversial. It has been recently suggested that transcriptional activity of p38 MAPK regulates the expression of peroxisome proliferator-activated receptor (PPAR)gamma, peroxisome proliferator activator receptor-gamma coactivator 1 (PGC-1),  and tricarboxylic acid cycle and oxidative phosphorylation mitochondrial genes (Aouadi et al. 2006; Crunkhorn et al. 2007). Similarly, JNK1 has been shown to regulate hepatic insulin signalling, mitochondrial biogenesis, fatty acid oxidation, oxidative phosphorylation, and TCA cycle (Yang and Trevillyan, 2008).

Understanding of the exact mechanism by which p38 MAPK leads to insulin resistance will hopefully assist in the development of targeted therapies. Inhibition of p38 MAPK as such would have multiple effects on plethora of cell signalling pathways. Therefore, it is of primary importance to identify down-stream targets of p38 MAPK that are directly linked with altered insulin-signalling pathways.

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