Hepatic Steatosis and Peroxisomal Fatty Acid Beta-oxidation

Three subhepatocellular compartments concur for fatty acids degradation including omega-oxidation in endoplasmic reticulum and beta-oxidation in both mitochondria and peroxisomes. Deficits affecting the peroxisomal physiology may be associated with multiple metabolic disturbances. Nowadays, a growing body of evidence underlines the key role of peroxisomal beta-oxidation in the sensing of lipid metabolism through the production/degradation of some essential metabolites. Lessons from several mice models strengthen the link between fatty acid beta-oxidation in peroxisomes and the nuclear hormone receptor Peroxisome Proliferator-Activated Receptor (PPAR)-alpha with an additional level of coregualtor complexity, which couples regulation of body energetic balance and hepatic caloric flux to functional peroxisome status. Here, we review key determinants of disrupted peroxisomal beta-oxidation pathway, which in liver promotes hepatic steatosis and hepatocarcinogenesis.