The epigenetic mechanisms of Non-Alcoholic Fatty Liver Disease

Background to the research: 

A quarter of the population in developed countries have non-alcoholic fatty liver disease (NAFLD). This condition can develop into impaired liver function as non-alcoholic steatohepatitis (NASH). and eventually to liver fibrosis, cirrhosis and liver failure or cancer. The initial driver of this disease pathway is an increased storage of fat in the liver which is linked to the high energy diets consumed in the 21st Century, and is associated with metabolic diseases such as type 2 diabetes and obesity.

The epigenome is the interface between genes and the environment. Therefore, epigenetic changes are integral to a cell’s response to diet, drugs, disease and interventions. The strong links between diet and the epigenome are evidenced by the shared molecules of energy metabolism and epigenetic regulation, which ensures that there is constant ‘communication’ between the two processes.

My laboratory aims to reveal the roles that epigenetics has in the initiation and progression of NAFLD to more severe liver disease. Additionally, we are exploring the potential for modulation of epigenetic mechanisms themselves to be a therapy.

Projects utilise in-vitro and rodent models for dissection of pathological mechanisms and novel therapy testing.

Cooperation with clinical colleagues in the UK and abroad is targeted at understanding the role of epigenetics and therapy in patient samples, and for uncovering novel biomarkers.

Collaborations with other researchers at the Institute of Hepatology aim to uncover the role of epigenetics in other liver diseases such as alcoholic liver disease, viral hepatitis and liver cancer.

 

Contact Dr Neil Youngson:  n.youngson@researchinliver.org.uk

 

Key collaborators:

Prof. Luca Valenti, University of Milan, Italy; Prof. Margaret Morris, UNSW Sydney, Australia; Prof. Nigel Turner, UNSW Sydney, Australia; Prof. Bill Ballard, UNSW Sydney, Australia

 

Key publicatons:

Morris MJ, Hesson LB, Poulos RC, Ward RL, Wong JWH, Youngson NA. Reduced nuclear DNA methylation and mitochondrial transcript changes in adenomas do not associate with mtDNA methylation. Biomarker Research. 2018. Dec 29;6:37

Aw WC, Towarnicki SG, Melvin RG, Youngson NA, Garvin MR, Hu Y, Nielsen S, Thomas T, Pickford R, Bustamante S, Vila-Sanjurjo A, Smyth GK & Ballard JWO. Diet influences metabolic flexibility and mitochondrial metabolism in Drosophila. PLoS Genetics. 2018. 6;14(11):e1007735

Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise. Scientific Reports. 2017. 8;7(1):15063

Youngson NA, Morris MJ, Ballard JWO. The mechanisms mediating the antiepileptic effects of the ketogenic diet, and potential opportunities for improvement with metabolism-altering drugs. Seizure. 2017. 52:15-19

Castino M, Baker-Andresen D, Ratnu V,  Shevchenko G, Morris, K, Bredy T, Youngson N, Clemens K. Persistent histone modifications at the BDNF and Cdk-5 promoters following extinction of nicotine-seeking in rats. Genes Brain and Behavior. 2017. doi: 

Published by: Foundation for Liver Research

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