Figure 1.

Reciprocal regulation of PPARα and autophagy-lysosomal signaling. (A) Induction of PPARα leads to increased transcription of autophagy (Atg) genes through either direct binding of PPARα to their promoter or through secondary regulation of TFEB levels. Induction of autophagy genes leads to engulfment of intrahepatic lipid droplets by autophagosomes and their eventual hydrolysis in lysosomal compartment termed as “lipophagy”. The free fatty acids released from lysosomes serve as substrate for mitochondrial β-oxidation further induced by PPARα leading to energy generation; (B) Impairment of autophagy-lysosomal activity leads to increased stability of PPARα corepressor NCoR1 as well as decreased stability of PPARα coactivator PGC1α leading to suppression of PPARα transactivation activity and reduced lipid catabolism in liver cells. The dotted up and down arrows denotes increase or decrease in levels.