Student research project
This project has the potential to identify a new therapeutic strategy to prevent insulin resistance and progression to type 2 diabetes.
The Metabolomics Laboratory uses state-of-the-art tandem mass spectrometry to obtain metabolic/lipid profiles from cell and animal models in addition to clinically relevant human samples to develop new approaches to diagnosis, risk assessment and therapy for diabetes and cardiovascular disease.
We have recently identified that phospholipid species containing odd carbon and branched chain fatty acids show a strong negative association with obesity1 and type 2 diabetes2. Previous studies have also identified a positive association between branched chain amino acids and type 2 diabetes3. These fatty acid species are metabolically linked to the catabolic pathway of branched chain amino acids and a potentially causal pathway has recently been highlighted using Mendelian randomization studies4. However, we do not understand whether an increase in branched chain amino acids, a decrease in branched chain fatty acids or a combination of both contributes to the development of type 2 diabetes.
Figure: Metabolic pathway linking branched chain amino acids with branched chain fatty acids.
We hypothesis that modulation of the branched chain catabolic pathway linking to the biosynthetic pathway of branched chain fatty acids will influence the onset of insulin resistance.
This project is suitable for an Honours or PhD student and we will use cell culture and animal models to investigate the relationship between branched chain amino acids and branched chain fatty acids with insulin resistance, glucose tolerance and type 2 diabetes.
- Plasma lipid profiling in a large population-based cohort J Lipid Res 2013;54(10):2898–908.
- Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes PloS one 2013;8(9):e74341.
- Metabolite profiles and the risk of developing diabetes Nat Med 2011;17(4):448–53.
- Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes: a mendelian randomisation analysis PLoS Med 2016;13(11):e1002179.