NAFLD project

Overconsumption of highly processed ready-made food, which is rich in refined sugars and saturated fatty acids, is directly implicated in the surge of NAFLD encompassing nonalcoholic steatohepatitis (NASH) are now among the most prevalent diseases (currently 9-37% incidence worldwide), with particularly steep increases in Western Societies that are likely lifestyle-related. Currently it affects 23% of the European Union population. NAFLD starts as an excessive accumulation of fat (steatosis) and then can progress to NASH and into more severe stages: fibrosis, cirrhosis and hepatocellular carcinoma. It is postulated that the progression of NAFLD towards NASH in a nonreversible manner requires an additional insult, possibly involving a pro-oxidative state and mitochondrial dysfunction. Although several studies have associated a pro-oxidative state with NAFLD, the sequence of events and the signaling pathways that link oxidative stress at the first stages of NAFLD progression are poorly characterized. Furthermore, the prospects of reversing NAFLD are considerably diminished once NASH is well established, but to this point of disease progression, NAFLD is responsive to both diet/lifestyle and therapeutic strategies. Nevertheless, no pharmacological consensus for NAFLD treatment currently exists, mainly because the stage in which the disease has progressed to a “point-of-no-return” remains unknown. Co- supplementation of the high-fat combined with high-sucrose diet closely mirrors Human Western Diet in terms of fat and sucrose content, which is characteristic for the eating habits of Western society.

Our research plans are dedicated to disclose the hepatic redox alterations and the specific end-points for mitochondrial dysfunction that represent a point of no return and which drive the progression of NAFLD towards NASH in a nonreversible manner. The proposed research topic addresses many conceptually exciting and fundamental questions, such as:

· What are the molecular mitochondrial mechanisms underlying NAFLD progression?

· Is there a particular oxidation pathway that underlies the pathogenesis of NAFLD and its progression?

· Is there a possibility by modulating oxidative stress to protect against or slow down development or progression of NAFLD?

· What is the impact of the Western diet on the lipid profile of mitochondrial membranes?