- Critical Evaluation of a Journal Article
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