Differential Regulation of Carnitine Palmitoyltransferase-I Gene Isoforms (CPT-I α and CPT-Iβ ) in the Rat Heart

Carnitine palmitoyltransferase-I (CPT-I) is a major control point for fatty acid oxidation. Two kinetically different isoforms, CPT-I α and CPT-I β, have been identified. Cardiac ventricular myocytes are the only cells known to express both CPT-I isoforms. In this study, we characterized the differential regulation of CPT-Iα and CPT-I β expression in the heart. Expression of the CPT-I α gene was very high in the fetal heart and declined following birth. CPT-I β was also highly expressed in fetal myocytes and remained so throughout development. CPT-I α mRNA abundance was increased in both the liver and heart of diabetic or fasted rats, but CPT-I β mRNA levels were not altered in these states. A high fat diet elevated expression of the CPT-Iα gene in the liver but not in the heart. The fat content of the diet did not affect the expression of CPT-Iβ . Cultures of neonatal rat cardiac myocytes were transfected with luciferase reporter genes driven by CPT-Iα or CPT-I β promoters. Two regions of the CPT-I α promoter, including an upstream region (−1300/−960) and a region in the proximal promoter (−193/−52) contributed equally to basal expression in cardiac myocytes. Basal transcription of CPT-I α was dependent on Sp1 sites and a CCAAT box in the proximal promoter. Our data indicate that the CPT-I β gene is expressed in a tissue specific manner, but that it is not subject to the same developmental or hormonal controls imposed on CPT-I α. In addition some aspects of CPT-Iα expression are confined to the liver. The data presented here thus suggest that two types of differential regulation of CPT-I genes exist: (a) differential control of CPT-I α and CPT-I β gene expression in the heart and (b) differential regulation of CPT-I α expression in the heart and liver.