Mechanisms of Hepatocyte Injury and Inflammation in NAFLD

Hepatocellular injury and inflammation are key features of NAFLD. Hepatocellular injury and death lead to inflammatory responses in the liver such as inflammasome activation and the recruitment of pro-inflammatory monocyte-derived macrophages and adaptive immune cells to form a sterile inflammatory environment in the liver. Bioactive toxic lipids such as free fatty acids, cholesterol and sphingo lipids accumulate in steatotic hepatocytes and activate cell stress and death pathways. Recent studies have elucidated how subsets of immune cells mediate liver inflammation. This chapter discusses the mechanisms, consequences and modulators of lipotoxicity and how they result in liver injury and inflammation. The role of interorgan cross talk, specifically gut–liver and adipose tissue–liver communication in mediating NAFLD pathogenesis is also discussed.