Exploring liver and adipose tissue alterations in the natural course of non-alcoholic fatty liver disease: A lipidomic Approach

Identifier:  TDX:4164

Handle: https://hdl.handle.net/20.500.11797/TDX4164

Authors:  Baiges Gaya, Gerard

Abstract:
Obesity is a worldwide health concern in which 60-90% of patients will develop the non-alcoholic fatty liver disease (NAFLD), the main hepatic manifestation of metabolic syndrome. Considering the importance of lipid metabolism and adipose tissue function for the development of metabolic disorders, in the present thesis, we aimed at elucidating the contribution of lipids to non-alcoholic steatohepatitis (NASH) development, characterizing the hepatic and adipose tissue lipidome in the context of obesity and diabetes as well as identifying the drivers involved in the NASH resolution under caloric restriction combined with metformin. Thus, C57BL/6J male mice were fed with a standard chow diet (CD), high-fat diet, and high-fat high sucrose diet (HFHSD) for 20 weeks to develop a mouse model associated with the diagnosis of NASH. After that, we used the NASH mouse model to explore the age-related effects and to test the metformin effectiveness in the prevention of NASH. Moreover, we investigated the effects of caloric restriction on NASH resolution as well as the synergic effects in combination with metformin. Our studies showed that HFHSD-fed mice develop NASH after 20 weeks of dietary treatment and they can be a good mouse model to recapitulate the metabolic disorders observed in patients with NASH. We also found that metformin should not be used as a preventive strategy for NASH. However, this pharmaceutical compound could be useful to potentiate the metabolic effects of caloric restriction.