Role of metabolic overload and metabolic inflammation in the development of Nonalcoholic Steatohepatitis (NASH)

Liang, W. (2015)

Doctoral Thesis

Overload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of pathologies that range from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis. The pathogenesis of NAFLD, including the sequence of events in time and the underlying mechanisms that initiate the transition from a fatty liver to NASH and fibrosis, remain poorly understood. Effective and reliable therapeutic approaches that are based on the understanding of the pathogenesis of NASH are therefore still lacking. In order to gain more insight into the mechanisms of NASH pathogenesis, we started with comparison of human NASH and experimental NASH. Subsequently, we provided evidence that activation of AP-1 and associated neutrophil infiltration is important for NAFL progression towards NASH and this can be induced experimentally by __metabolic__ dietary triggers of inflammation.Furthermore, we explored novel nutritional and pharmacological agents as potential strategies to combat NASH. Finally, we investigated the effects of high fat diet-induced metabolic overload on the liver in relation to inflammation in white adipose tissue and kidney, and the dysfunction of these tissues.

• Transcription factors
• Chronic inflammation
• Factors
• Pathogensis
• Histology
• NAFLD/NASH
• Fibrosis
• Dyslipidemia
• Insulin resistance
• Fatty liver
• Metabolic syndromes

• All authors: Liang, W.
• Supervisor: Havekes, L.M.
• Co-supervisor: Hoek, A.M. van den; Kleemann, R.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2015-03-31
• ISBN (print): 9789461089205