Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors primarily involved in lipid homeostasis. PPARdelta displays strong expression in tissues with high lipid metabolism, such as adipose, intestine and muscle. Its role in skeletal muscle remains largely unknown. After a 24-h starvation period, PPARdelta mRNA levels are dramatically up-regulated in gastrocnemius muscle of mice and restored to control level upon refeeding. The rise of PPARdelta is accompanied by parallel up-regulations of fatty acid translocase/CD36 (FAT/CD36) and heart fatty acid binding protein (H-FABP), while refeeding promotes down-regulation of both genes. To directly access the role of PPARdelta in muscle cells, we forced its expression and that of a dominant-negative PPARdelta mutant in C2C12 myogenic cells. Differentiated C2C12 cells responds to 2-bromopalmitate or synthetic PPARdelta agonist by induction of genes involved in lipid metabolism and increment of fatty acid oxidation. Overexpression of PPARdelta enhanced these cellular responses, whereas expression of the dominant-negative mutant exerts opposite effects. These data strongly support a role for PPARdelta in the regulation of fatty acid oxidation in skeletal muscle and in adaptive response of this tissue to lipid catabolism.
Holst
Dorte
D
Inserm U470, Institut de Recherche Signalisation, Biologie du Développement et Cancer, Centre de Biochimie, Faculté des Sciences, Parc Valrose, Université de Nice, 06108 Nice, France.
Luquet
Serge
S
Nogueira
Véronique
V
Kristiansen
Karsten
K
Leverve
Xavier
X
Grimaldi
Paul A
PA
D000818:Animals; D002250:Carbon Radioisotopes; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D009154:Mutation; D009747:Nutritional Physiological Phenomena; D010168:Palmitates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D010168:Palmitates; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C022776:2-bromopalmitate