Overexpression of peroxisome proliferator-activated receptor gamma coactivator-1alpha down-regulates GLUT4 mRNA in skeletal muscles.
Exercise training increases mitochondria and GLUT4 in skeletal muscles. Recent studies indicate that an increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) by exercise may promote mitochondrial biogenesis and fatty acid oxidation. To examine whether increased PGC-1alpha expression was also responsible for an increase of GLUT4 expression, transgenic mice that overexpress PGC-1alpha in skeletal muscles driven by a human alpha-skeletal actin promoter were made. PGC-1alpha was overexpresssed in skeletal muscles including type I and II fiber-rich muscles but not in the heart. With an increase of PGC-1alpha mRNA, type II fiber-rich muscles were redder, and genes of mitochondrial oxidative metabolism were up-regulated in skeletal muscles, whereas the expression of GLUT4 mRNA was unexpectedly down-regulated. In parallel with a decrease of GLUT4 mRNA, an impairment of glycemic control after intraperitoneal insulin administration was observed. Thus, an increase of PGC-1alpha plays a role in increasing mitochondrial biogenesis and fatty acid oxidation but not in increasing GLUT4 mRNA in skeletal muscles.
Miura
Shinji
S
Division of Clinical Nutrition, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Kai
Yuko
Y
Ono
Misaki
M
Ezaki
Osamu
O
D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D004579:Electron Transport / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D005947:Glucose