An overview of deregulated lipid metabolism in nonalcoholic fatty liver disease with special focus on lysosomal acid lipase

Abstract

Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD. In this review, we provided a comprehensive overview of the critical steps in hepatic fat metabolism and alterations in these pathways in NAFLD, with a special focus on lipophagy and LAL activity. During NAFLD, hepatic fat metabolism is impaired at several levels, which is significantly contributed to by impaired lipophagy, in which reduced LAL activity may play an important role. For further research and intervention in NAFLD, targeting LAL activity may provide interesting perspectives.