Project 4

Progressive loss of contractile muscle mass and function (sarcopenia) is commonly accompanied by an increase of ectopic skeletal muscle fat infiltration (myosteatosis). The accumulation of intermuscular adipose tissue (IMAT) interdigitated between muscle fibres beneath the muscle fascia represents a negative prognostic factor for several myopathies, cardio-metabolic diseases, diabetes and cancer. Evidence that accelerated myosteatosis occurs in people with obesity and diabetes further points to a main underlying mechanism by which chronic diseases cause physical disability and increase mortality. In the context of metabolic disease progression and remission potential determinants of myosteatosis have not been clearly defined and numerous gaps in the understanding of the pathophysiologic mechanisms that compromise muscle health and disrupt metabolism persist. We recently reported that human IMAT has a unique gene expression pattern distinct from subcutaneous fat and skeletal muscle and directly modulates skeletal muscle insulin sensitivity. We hypothesize herein that computational integration of distinctive innovative non-invasive optoacoustic microscopy (MiROM), multispectral optoacoustic tomography (MSOT) and MRI imaging patterns with region specific cellular compositions, spatial gene expression patterns and key metabolic fluxes of IMAT visualizes changes in human IMAT in response to lifestyle interventions. With this approach we aim to develop a standardized tool for the non-invasive assessment of metabolic disease and the prediction of its progression or remission under personalized treatment strategies in humans.