| First Author | Jo E | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 4 | Pages | e0173676 |
| PubMed ID | 28422956 | Mgi Jnum | J:246525 |
| Mgi Id | MGI:5917864 | Doi | 10.1371/journal.pone.0173676 |
| Citation | Jo E, et al. (2017) Chronic activation of PPARalpha with fenofibrate reduces autophagic proteins in the liver of mice independent of FGF21. PLoS One 12(4):e0173676 |
| abstractText | Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARalpha may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARalpha with fenofibrate (FB) in mice. Chronic administration of the PPARalpha agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62. This was concomitant with an increase in the expression of lipogenic proteins mSREBP1c, ACC, FAS and SCD1. These effects of FB were completely abolished in PPARalpha-/- mice but remained intact in mice with global deletion of FGF21, a key downstream mediator for PPARalpha-induced effects. Further studies showed that decreased the content of autophagy proteins by FB was associated with a significant reduction in the level of FoxO1, a transcriptional regulator of autophagic proteins, which occurred independently of both mTOR and Akt. These findings suggest that chronic stimulation of PPARalpha may suppress the autophagy capacity in the liver as a result of reduced content of a number of autophagy-associated proteins independent of FGF21. |
