Thyroid hormone regulates carnitine palmitoyltransferase Ialpha gene expression through elements in the promoter and first intron.

Carnitine palmitoyltransferase I (CPT-I) catalyzes the transfer of long chain fatty acyl groups from CoA to carnitine for translocation across the mitochondrial inner membrane. CPT-Ialpha is a key regulatory enzyme in the oxidation of fatty acids in the liver. CPT-Ialpha is expressed in all tissues except skeletal muscle and adipose tissue, which express CPT-Ibeta. Expression of CPT-Ialpha mRNA and enzyme activity are elevated in the liver in hyperthyroidism, fasting, and diabetes. CPT-Ialpha mRNA abundance is increased 40-fold in the liver of hyperthyroid compared with hypothyroid rats. Here, we examine the mechanisms by which thyroid hormone (T3) stimulates CPT-Ialpha gene expression. Four potential T3 response elements (TRE), which contain direct repeats separated by four nucleotides, are located 3000-4000 base pairs 5' to the start site of transcription in the CPT-Ialpha gene. However, only one of these elements functions as a TRE. This TRE binds the T3 receptor as well as other nuclear proteins. Surprisingly, the first intron of the CPT-Ialpha gene is required for the T3 induction of CPT-Ialpha expression, but this region of the gene does not contain a TRE. In addition, we show that CPT-Ialpha is induced by T3 in cell lines of hepatic origin but not in nonhepatic cell lines.