Defining the link between hepatic NAD+ salvage capacity and liver fibrosis at Novo Nordisk Foundation Center for Basic Metabolic Research

Posted 1 week ago

This is a project proposal for a student opportunity at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR).
Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as a global pandemic as the prevalence of obesity and type 2 diabetes (T2D) increases worldwide. NAFLD can progress to non-alcoholic steatotic hepatitis (NASH) with associated fibrosis, and can further progress to cirrhosis and hepatocellular carcinoma. NAFLD is prevalent in T2D patients as >70% show signs of the disease with 20% progressing into NASH. No treatment for NASH currently exists, so novel treatments are needed. Increasing NAD+ levels is an effective treatment for reducing hepatic lipid accumulation in rodent models for obesity. In the liver, NAD+ levels are largely maintained by the NAD+ salvage enzyme nicotinamide phosphoribosyltransferase (NAMPT). Our preliminary data show that hepatocyte-specific Nampt knockout (HNKO) mice alterations in bile acid metabolism and develop hepatic fibrosis with focal necrosis and portal inflammation.

The project: The over-arching goal of this project is to understand the link between impaired NAD+ salvage capacity and liver fibrosis to provide novel insights into treatments for hepatic fibrosis/NASH. We have performed both transcriptomic and proteomic analyses of samples from HNKO mice and wild type littermate controls. Information from these data sets will be extracted, and we will design experiments to determine causality between specific genotype/phenotype interactions observed.

The student: You are highly motivated and excited to learn about liver biology in relation to NAD+ metabolism.

Contact: Please contact Associate Professor Jonas Treebak (jttreebak@sund.ku.dk) for more information related to this project.

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