University of Cambridge > > Babraham Seminar > Liver Lipid Metabolism and Healthy Ageing: Themes from the Drug Discovery Frontline

Liver Lipid Metabolism and Healthy Ageing: Themes from the Drug Discovery Frontline

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One in three of us will die from a cardiometabolic disease, with current primary treatments directly targeting liver metabolism to lower blood lipids and blood glucose. It turns out that high blood glucose (due to insulin resistance and type 2 diabetes) correlates with the quantity and types of lipids stored in the liver, placing liver lipid metabolism at the centre of human cardiometabolic maladies. Fatty liver affects one in four of us, dramatically increasing in prevalence with age and obesity. In addition to affecting cardiometabolic healthspan, this excess fat can trigger a metabolic stress response in the liver itself, resulting in cell damage, inflammation (called non-alcoholic steatohepatitis: NASH ), and cirrhosis. In Europe, liver cirrhosis is one of the top ten causes of death. It is the main indication for liver transplantation, with NASH now emerging as its leading aetiology over alcohol and viral hepatitis. Worryingly, whilst many patients die waiting for a donor, even mildly NASH donor livers are discarded because these are particularly sensitive to the hypoxic metabolic stress that occurs with transplantation. With no on-label therapies and an expected market of over US$10 billion within five years, fatty liver has prompted considerable R&D investment. As Head of the Cellular and Systems Genomics department for the newly formed Novo Nordisk Research Centre Oxford – a hybrid industry-academic research institute – my team and I have used biobanks, in vitro liver organoids, and even perfused ex vivo whole human livers to identify druggable fatty liver targets. With some surprising themes.

This talk is part of the Babraham Seminar series.

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