Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPAR alpha has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPAR alpha transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPAR alpha nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPAR alpha nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).