title: PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype.
abstract: Peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta (PGC-1alpha and PGC-1beta) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism were studied from days 5 to 22 of culture. PGC-1alpha and PGC-1beta overexpression caused a three- to fourfold increase in mRNA level, a doubling of enzymatic activity of citrate synthase, a slight increase in short-chain acyl-CoA dehydrogenase mRNA, a doubling of the mRNA level, and a 30-50% increase in enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase. Lactate dehydrogenase or creatine kinase activity was unchanged. PGC-1alpha enhanced glycogen buildup twofold at 5 or 25 mM glucose, whereas PGC-1beta caused a decrease. Both PGC-1alpha and PGC-1beta overexpression caused a faster maturation of myotubes, as seen by mRNA downregulation of the immature embryonal and perinatal myosin heavy-chain (MHC) isoforms. PGC-1alpha or PGC-1beta overexpression enhanced mRNA of the slow oxidative-associated MHC isoform MHCIb and downregulated mRNA levels of the fast glycolytic-associated MHC isoforms MHCIIX and MHCIIB. Only PGC-1beta overexpression caused an increase in mRNA of the intermediary fast oxidative-associated MHC isoform MHCIIA. PGC-1alpha or PGC-1beta overexpression upregulated GLUT4 mRNA and downregulated myocyte enhancer factor 2C transcription factor mRNA; only PGC-1alpha overexpression caused an increase in the mRNA expression of TRB3, a negative regulator of insulin signaling. These results show that both PGC-1alpha and PGC-1beta are involved in the regulation of skeletal muscle fiber transition and metabolism and that they have both overlapping and differing effects.
authors.affiliation: Department of Medical Biochemistry and Genetics, University of Copenhagen, Blegdamsvej 3, Bldg. 6.5, DK-2200 N, Denmark.
authors.forename: Ole Hartvig
authors.initials: OH
authors.lastname: Mortensen
authors.forename: Lis
authors.initials: L
authors.lastname: Frandsen
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Erica
authors.initials: E
authors.lastname: Nishimura
authors.forename: Niels
authors.initials: N
authors.lastname: Grunnet
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000502:physiology; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000235:genetics; D006003:Glycogen / Q000378:metabolism; D064326:MEF2 Transcription Factors; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; C502443:Trib3 protein, rat; D006003:Glycogen; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D018995:Myosin Heavy Chains