An increase in prevalence of metabolism-associated disorders worldwide poses an enormous financial burden on our current medical systems globally. This cluster of disorders includes obesity, insulin resistance, hypertension and coronary artery disease, collectively known as the metabolic syndrome disorders. The underlying pathogenesis is often attributed to interactions between genetic and environmental factors. Reliable biomarkers for early detection of these complex disorders have remained elusive.
This project utilises genome-wide expression profiling in an attempt to identify high level interactions between genes and regulatory pathways in ACTH-treated and compared with saline-treated Sprague-Dawley rats. This ACTH rodent model has been shown to exhibit traits and phenotypic manifestations of these disorders similar to those observed in humans.
We have identified specific differential gene expression signatures as a result of ACTH administration. Gene annotation analyses have mapped those genes to a variety of cellular functions including signal transduction, carbohydrate/lipid metabolism, and cell organization and biogenesis. Interestingly, the majority of novel genes identified was mapped onto pathways involved in the signalling networks of insulin resistance and exerts an effect on regulation of intermediary metabolism and cell organization. The significance of this work is two fold; firstly, use of transcriptome based profiling at genomic level is feasible in identifying genetic signatures in these disorders, as is observed in oncology research and secondly, identification of novel candidate genes and networks associated with these disorders elucidate regulatory pathways that have potential to be developed further in clinical settings.
Future work aims to address difference between ACTH-induced hypertension and dexamethasone-induced hypertension in the Sprague-Dawley rat model, and candidate gene studies. This branch of projects is in collaboration with Prof. Judith Whitworth and Dr Yi Zhang at the John Curtin Medical School, ANU, Canberra.
