Non-Alcoholic Fatty Liver Disease – new insights in development and treatment
In this project we investigated different conceptual innovative therapeutical approaches for their ability to reduce Non-Alcoholic Fatty Liver Disease (NAFLD) and elucidated underlying disease-causing processes. This provides the research community, among which the consortium partners, new insights and knowledge about the development of NAFLD and novel treatment strategies.
NAFLD is the most common form of chronic liver disease, with an estimated prevalence ranging from 25% to 40% worldwide. The fatty liver can progress to liver cirrhosis and cancer with high mortality rates and is an important risk factor for chronic diseases such as type 2 diabetes and cardiovascular disease. There is an urgent need for more knowledge about underlying disease-causing processes and new therapeutic treatments.
This project aimed to gain new insights and knowledge about the development of NAFLD and the sequence in which underlying disease-causing processes occur in the gut, adipose tissue and liver and to test new treatment strategies for their ability to reduce the development of NAFLD. Hereto a number of studies have been performed with Low Density Lipoprotein Receptor (Ldlr)-/-.Leiden mice that, fed a high-fat diet, develop NAFLD comparable to that of humans. High-fat diet foods caused adipose tissue inflammation and increased intestinal permeability prior to liver inflammation. The tested new conceptual nutritional or pharmaceutical treatments decreased to a lesser or greater extent liver fattening, inflammation and fibrosis.
This project has shown that adipose tissue and intestinal dysfunction precede the development of liver inflammation and liver fibrosis. Multiple organs contribute to the development of NALFD and this organ-organ crosstalk can be exploited to the benefit of patients, namely to slow down disease progression. Several innovative therapeutic treatments resulted in beneficial effects on one or more causal mechanisms underlying NAFLD and support a combination of specific nutritional and pharmaceutical approaches in the future.
