Obesity related systemic inflammation as a driver of Non-alcoholic fatty liver disease

Non-alcoholic fatty liver (NAFLD) disease effects more than 80% of obese patients. This disease is gaining increasing attention as independent driver of liver related morbidity and cardiovascular disease. It is closely related to insulin resistance and the metabolic syndrome. Simple steatosis has few direct adverse effects, however, inflammation and fibrosis are more strongly linked with morbidity and mortality. The pathophysiology of NAFLD is poorly understood. It remains unclear whether peripheral visceral or subcutaneous adipose tissue drives NAFLD, or if NALFD itself plays a key role in primarily driving insulin resistance. A systemic inflammatory response, associated with excess adipose tissue stores is thought to drive many key features of metabolic dysfunction and cardiovascular risk. This study will evaluate the correlation of adipose and systemic inflammation with the extent of liver damage associated with NAFLD and seeks to better understand the primary driving site of liver damage. In this study, a cohort of 150 obese patients have been recruited into a larger prospective study. Serum, liver tissue, subcutaneous and visceral fat samples have been stored. Analysis will seek to describe the inflammatory response in each of these depots using a variety of techniques. Quantitative real-time PCR was performed on adipose tissue samples to determine mRNA expression of IL-6, IL-1, TNF- and CCL2. Serum samples will undergo ELISA to quantify concentrations of IL-6, IL-1β, CCL2 and TNF-α. Follow up serum collections associated with weight loss will be similarly analysed. This study study is suitable for an honours project, which would focus on characterising inflammation in collected tissue samples. This could easily be extended to a PhD which could involve collection of additional tissue specimens, lipidomic and protenomic analysis and correlation of animal models.