Diurnal variability in lipid and glucose handling in patients with non-alcoholic fatty liver disease (NAFLD): an experimental medicine and phosphoproteomics approach
Thomas Marjot, University of Oxford
Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population, is closely associated with insulin resistance, and confers an increased risk of hepatic and cardiovascular mortality. Despite circadian datasets demonstrating rhythmic control of genes involved in glucose and lipid metabolism, there have been no human studies exploring diurnal patterns in the functional pathways governing intrahepatic lipid accumulation
As part of a Doctoral degree, I am currently performing a clinical study in NAFLD patients which has already identified significant time-of-day variability in multiple pathogenic pathways. This travel grant seeks to build on this preliminary data by establishing a new international collaboration with immense training potential.
1) To establish whether diurnal differences in the pathways involved in NAFLD pathogenesis (e.g. insulin resistance, de novo lipogenesis, adipose lipolysis) can be explained by differential phosphoproteomic signatures in human skeletal muscle and adipose tissue.
2) To forge a collaborative partnership between the Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM), University of Oxford and The Systems Chronobiology Laboratory, Ludwig Maximilian University of Munich (LMU).
3) To allow Dr Thomas Marjot to visit LMU in order to learn state-of-the-art laboratory techniques relating to tissue proteomics as part of his Doctoral degree at the University of Oxford
4) To broaden Dr Marjot’s understanding of the use of mass spectrometry-based quantitative phosphoproteomics to study post-transcriptional and post-translational regulation of circadian mechanisms in human health and disease
Grant awarded: £1,970.00