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PPAR Research
Volume 2011, Article ID 256186, 10 pages
Research Article

Consequences of PPARα Invalidation on Glutathione Synthesis: Interactions with Dietary Fatty Acids

1INRA, UMR914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France
2AgroParisTech, UMR914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France
3INRA, UR66 ToxAlim, Laboratoire de Pharmacologie et Toxicologie, Toulouse, France

Received 26 April 2011; Revised 26 June 2011; Accepted 11 July 2011

Academic Editor: Stephane Mandard

Copyright © 2011 Najoua Guelzim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Glutathione (GSH) derives from cysteine and plays a key role in redox status. GSH synthesis is determined mainly by cysteine availability and γ-glutamate cysteine ligase (γGCL) activity. Because PPARα activation is known to control the metabolism of certain amino acids, GSH synthesis from cysteine and related metabolisms were explored in wild-type (WT) and PPARα-null (KO) mice, fed diets containing either saturated (COCO diet) or 18 : 3 n-3, LIN diet. In mice fed the COCO diet, but not in those fed the LIN diet, PPARα deficiency enhanced hepatic GSH content and γGCL activity, superoxide dismutase 2 mRNA levels, and plasma uric acid concentration, suggesting an oxidative stress. In addition, in WT mice, the LIN diet increased the hepatic GSH pool, without effect on γGCL activity, or change in target gene expression, which rules out a direct effect of PPARα. This suggests that dietary 18 : 3 n-3 may regulate GSH metabolism and thus mitigate the deleterious effects of PPARα deficiency on redox status, without direct PPARα activation.