Label-free imaging of lipid-glucose metabolism in cells, tissues, and animals

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Lipid and glucose metabolic plasticity and adaptation are associated with many pathological conditions, such as diabetes and obesity. However, the molecular and cellular mechanisms of metabolic flexibility and heterogeneity remains poorly understood – despite its relevance for the development of new therapeutic targets to alleviate metabolic disorders derived from maladaptive responses. Metabolic imaging allows obtaining spatio-temporal metabolic dynamic information from cellular to system level. In this way, metabolic imaging is a powerful approach to facilitate diagnosis and evaluate therapeutic response. However, most of the technologies available for metabolic imaging are restricted to be used in combination with exogenous labels or markers. These labels and markers have limited biodistribution, can potentially perturb normal response¬, or are simply not available. Mid-infraRed Optoacoustic Microscopy (MiROM) is a novel label-free imaging method based on direct vibrational excitation of biomolecules by mid-infrared light and optoacoustic detection. MiROM provides a unique opportunity for label-free, non-invasive, and longitudinal metabolic imaging to understand the metabolic dynamics and heterogeneity at single-cell level. Here, we propose to take advantage and further develop the non-invasive and label-free imaging capacity of MiROM to study the metabolic plasticity and functional heterogeneity of adipocytes and skeletal muscle cells. Our goal is to be able to interrogate mechanisms for improved metabolic flexibility in skeletal muscle and adipose tissue in order to bring new insights to the prevention, early diagnosis, treatment and management of diabetes and obesity. Additionally, we will explore whether non-invasive in vivo metabolic imaging in skin, using MiROM, reflects the overall metabolism status and can serve as an indicator of health and disease for personalized diagnostics. Our study will set the foundation for future phases of this project involving clinical transfer of MiROM technology for continuous metabolic monitoring of lipids and carbohydrates non-invasively in human.