Time-course effects of increased fatty acid supply on the expression of genes involved in lipid/glucose metabolism in muscle cells.
Fatty acid (FA) oversupply in skeletal muscle is related with metabolic disorders associated to obesity, and also with normal physiological responses. We studied, in vivo and in vitro, the chronological response to physiological increases of FA, analyzing the expression of selected genes important for glucose/lipid metabolism. An in vivo sequential model of fasting (known to increase circulating FA) and refeeding was used in male Wistar rats to study soleus (more oxidative) and gastrocnemius (more glycolytic) muscles, and a chronological study was made in C2C12 muscle cells under treatment of oleic/linoleic FA mixture, at physiological concentration. Body weight, muscle glycogen and blood parameters (glucose, insulin, free fatty acids -FFA-, triglycerides) were monitored. mRNA levels of muscle carnitine palmitoyl transferase 1 (mCPT1), GLUT 4, insulin receptor (InsR), MyoD1, peroxisome proliferator activated receptor (PPAR) gamma coactivator 1alpha (PGC1alpha) and beta (PGC1beta), PPARalpha, PPARdelta, pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling proteins (UCPs) 2 and 3 were analyzed by quantitative RT-PCR. The main results were the quick induction of PGC1alpha, UCP3 and PDK4 in vivo (more marked in gastrocnemius) and of PGC1alpha, PGC1beta, InsR, PDK4, UCP2 and UCP3 in vitro. It is concluded that FA are able to rapidly induce the expression in muscle cells of key genes involved in their catabolism and that the oleic/linoleic acid mixture has a positive role increasing the expression of master metabolic regulators and their downstream target genes, facilitating the transition from a more glycolytic to a more lipid-oxidative metabolism.
Rodríguez
Ana M
AM
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics). University of the Balearic Islands (UIB) and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 07122 Palma de Mallorca, Spain.
Sánchez
Juana
J
Tobaruela
Aixa
A
Priego
Teresa
T
Picó
Catalina
C
Palou
Andreu
A
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D019787:Linoleic Acid / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D051275:Glucose Transporter Type 4; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047494:PPAR delta; D047495:PPAR gamma; C000604391:Ucp2 protein, rat; C000604394:Ucp3 protein, rat; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D019301:Oleic Acid; D019787:Linoleic Acid; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D011972:Receptor, Insulin; D005947:Glucose