Hepatic Fasting-Induced PPARα Activity Does Not Depend on Essential Fatty Acids.
The liver plays a central role in the regulation of fatty acid metabolism, which is highly sensitive to transcriptional responses to nutrients and hormones. Transcription factors involved in this process include nuclear hormone receptors. One such receptor, PPARα, which is highly expressed in the liver and activated by a variety of fatty acids, is a critical regulator of hepatic fatty acid catabolism during fasting. The present study compared the influence of dietary fatty acids and fasting on hepatic PPARα-dependent responses. Pparα(-/-) male mice and their wild-type controls were fed diets containing different fatty acids for 10 weeks prior to being subjected to fasting or normal feeding. In line with the role of PPARα in sensing dietary fatty acids, changes in chronic dietary fat consumption influenced liver damage during fasting. The changes were particularly marked in mice fed diets lacking essential fatty acids. However, fasting, rather than specific dietary fatty acids, induced acute PPARα activity in the liver. Taken together, the data imply that the potent signalling involved in triggering PPARα activity during fasting does not rely on essential fatty acid-derived ligand.
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Arnaud.Polizzi@toulouse.inra.fr.
Arnaud
A
Polizzi
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Edwin.Fouche@toulouse.inra.fr.
Edwin
E
Fouché
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. simon.ducheix@yahoo.fr.
Simon
S
Ducheix
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Frederic.Lasserre@toulouse.inra.fr.
Frédéric
F
Lasserre
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. alice.p.marmugi@gmail.com.
Alice P
AP
Marmugi
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Laila.Lakhal@toulouse.inra.fr.
Laila
L
Mselli-Lakhal
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Nicolas.Loiseau@toulouse.inra.fr.
Nicolas
N
Loiseau
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Walter.Wahli@ntu.edu.sg.|Lee Kong Chian School of Medicine, Nanyang Technological University, 637553 Singapore, Singapore. Walter.Wahli@ntu.edu.sg.|Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Walter.Wahli@ntu.edu.sg.
Walter
W
Wahli
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Herve.Guillou@toulouse.inra.fr.
Hervé
H
Guillou
INRA ToxAlim, 180, Chemin de Tournefeuille, 31027 Toulouse Cedex 3, France. Alexandra.Montagner@toulouse.inra.fr.
Alexandra
A
Montagner
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4 / Q000235:genetics; D004041:Dietary Fats; D005215:Fasting; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
C512110:Cyp4a10 protein, mouse; C436963:Cyp4a14 protein, mouse; D004041:Dietary Fats; D047493:PPAR alpha; D012333:RNA, Messenger; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D000072470:Cytochrome P450 Family 4; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
PPARα; dietary fatty acids; fasting; nuclear receptors; polyunsaturated fatty acids; steatosis
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