Bioactive signalling lipids as drivers of chronic liver diseases

Abstract

Lipids are important in multiple cellular functions, with most having structural or energy storage roles. However, a small fraction of lipids exert bioactive roles through binding to G protein-coupled receptors and induce a plethora of processes including cell proliferation, differentiation, growth, migration, apoptosis, senescence and survival. Bioactive signalling lipids are potent modulators of metabolism and energy homeostasis, inflammation, tissue repair and malignant transformation. All these events are involved in the initiation and progression of chronic liver diseases. In this review, we focus specifically on the roles of bioactive lipids derived from phospholipids (lyso-phospholipids) and poly-unsaturated fatty acids (eicosanoids, pro-resolving lipid mediators and endocannabinoids) in prevalent chronic liver diseases (alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis and hepatocellular carcinoma). We discuss the balance between pathogenic and beneficial bioactive lipids as well as potential therapeutic targets related to the agonism or antagonism of their receptors.

Keywords: ALD; G protein coupled receptors; HCC; NAFLD; Poly-unsaturated fatty acid lipid mediators; eicosanoids; liver cancer; liver fibrosis; lyso-phospholipids; steatohepatitis; viral hepatitis.