BIOCHEMICAL IMAGING · Fatty acid processing and metabolism in muscle cells revealed by non-linear vibrational imaging

Fatty acid processing and metabolism in muscle cells revealed by non-linear vibrational imaging.

Fatty acid (FA) uptake and its subsequent fate are implicated the two most prevalent diseases in the developed world, coronary heart disease and type 2 insulin-resistant diabetes. More than 300 million people world-wide live with type 2 diabetes and its incidence is increasing rapidly, especially in developing countries (WHO http://www.who.int/mediacentre/factsheets/fs312/en/index.html). In Europe alone, direct medical expenses for type 2 diabetes totals more than 30 Billion € per year, and more than 50% of these costs are related to hospitalization. To reduce these costs and increase the quality of life, better candidates for therapeutic intervention and diagnosis through improved understanding of mechanisms causing type 2 diabetes are required. The aim of this research project is to develop new biophysical and imaging tools based on local chemical imaging using coherent anti-Stokes Raman scattering (CARS) microscopy for mechanistic studies of FA trafficking and metabolism in muscle. Muscle is a common site for lipid deposition from excessive fat intake in the form of lipid droplets (LDs). In most people, such muscle lipid droplets are typically precursors to downstream insulin resistance and type 2 diabetes whereas they are benign for endurance-trained athletes. A key question lies in why lipid deposits in athletes do not lead to pathogenesis. This requires a reliable, straightforward method quantify local biochemistry within intact tissue samples. The spatio-chemical imaging methods developed in this project combined with relevant cellular models have allowed us to directly quantify differences in protein and lipid species within muscle tissues and cells and to further explore how biochemistry of lipid inclusions are related with insulin resistance.

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