Peroxisomal proliferator activated receptor gamma coactivator (PGC-1alpha) stimulates carnitine palmitoyltransferase I (CPT-Ialpha) through the first intron.
Peroxisomal proliferator activated receptor gamma coactivator-1 (PGC-1alpha) is a transcriptional coactivator that promotes mitochondrial biogenesis and energy metabolism in brown fat, skeletal muscle and heart. Previous studies demonstrated that PGC-1alpha is present at low levels in the liver but that the hepatic abundance of PGC-1alpha is elevated in diabetic and fasted animals. Elevated PGC-1alpha expression is associated with increased fatty acid oxidation and hepatic glucose production. Carnitine palmitoyltransferase-I (CPT-I) is a rate controlling step in the mitochondrial oxidation of long chain fatty acids. CPT-I transfers the acyl moiety from fatty acyl-CoA to carnitine for the translocation of long chain fatty acids across the mitochondrial membrane. There are two isoforms of CPT-I including a liver isoform CPT-Ialpha and a muscle isoform CPT-Ibeta. Here, we characterized the regulation of CPT-Ialpha isoform by PGC-1alpha. PGC-1alpha stimulates CPT-Ialpha primarily through multiple sites in the first intron. We found that PGC-1alpha can induce CPT-Ialpha gene expression in cardiac myocytes and primary hepatocytes. Our results indicate that PGC-1alpha elevates the expression of CPT-Ialpha via a unique mechanism that utilizes elements within the intron.
Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA.
Shulan
S
Song
Yi
Y
Zhang
Ke
K
Ma
Loretta
L
Jackson-Hayes
Eduard N
EN
Lavrentyev
George A
GA
Cook
Marshall B
MB
Elam
Edwards A
EA
Park
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D032342:Muscle Cells / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D002334:Carnitine O-Palmitoyltransferase