Abstract
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, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα 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 PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).
Highlights
Lipid homeostasis in cells is maintained via a balance of lipid anabolic and lipid catabolic events, which control lipid levels within the hepatic cells [1]
These findings suggest that there is an important crosstalk between lysosome function and PPARα genes involved in autophagy and peroxisomal activity, and vice versa (Figure 1B)
The novel connection between lysosomal function and peroxisomal gene transcription via PGC1α-PPARα nuclear receptor activity raises the possibility that peroxisomal activity can be enhanced by increasing lysosomal activity, especially in disorders linked to peroxisomal defects such as Neimann-Pick disease and X-linked adrenal leukodystrophy [58]
Summary
Lipid homeostasis in cells is maintained via a balance of lipid anabolic and lipid catabolic events, which control lipid levels within the hepatic cells [1]. Peroxisome proliferator-activated receptors (PPARs) are key regulators of hepatic lipid metabolism [3,4]. Several coactivator and corepressor proteins bind to PPAR/RXR heterodimers to further modulate their transcriptional activity [5] This PPAR/RXR regulates the expression of genes encoding enzymes or proteins involved in the mitochondrial and peroxisomal β-oxidation, fatty acid (FA) uptake, and lipolysis [6]. Proper lysosomal function was itself determining PPARα transcriptional activity by regulating the stability of its cofactor, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) [8] and nuclear receptor co-repressor 1 (NCoR1) [9]. We describe the interplay of this PPARα/lysosomal signaling, which mediates the homeostatic hepatic lipid metabolism
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
