Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle
Research output: Contribution to journal › Journal article › Research › peer-review
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.
|Journal||BBA General Subjects|
|Number of pages||8|
|Publication status||Published - 4 Jul 2003|
- Animals, Carbon Radioisotopes, Cell Differentiation, Cell Line, Fatty Acids, Gene Expression Regulation, Kinetics, Male, Mice, Mice, Inbred C57BL, Muscle, Skeletal, Mutation, Nutritional Physiological Phenomena, Palmitates, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Transcription Factors, Transcriptional Activation