Chronic activation of PPAR alpha with fenofibrate reduces autophagic proteins in the liver of mice independent of FGF21

Cheung, J, Li, S, Zhang, X, Wang, H, Herbert, T, Jenkins, T, Xu, A and Ye, J 2017, 'Chronic activation of PPAR alpha with fenofibrate reduces autophagic proteins in the liver of mice independent of FGF21', PLoS ONE, vol. 12, no. 4, e0173676, pp. 1-10.


Document type: Journal Article
Collection: Journal Articles

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Title Chronic activation of PPAR alpha with fenofibrate reduces autophagic proteins in the liver of mice independent of FGF21
Author(s) Cheung, J
Li, S
Zhang, X
Wang, H
Herbert, T
Jenkins, T
Xu, A
Ye, J
Year 2017
Journal name PLoS ONE
Volume number 12
Issue number 4
Article Number e0173676
Start page 1
End page 10
Total pages 10
Publisher Public Library of Science
Abstract This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα 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 PPARα-/- mice but remained intact in mice with global deletion of FGF21, a key downstream mediator for PPARα-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 PPARα may suppress the autophagy capacity in the liver as a result of reduced content of a number of autophagyassociated proteins independent of FGF21.
Subject Metabolic Medicine
DOI - identifier 10.1371/journal.pone.0173676
Copyright notice © 2017 Jo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN 1932-6203
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