Regulation of fatty acid transport protein and mitochondrial and peroxisomal beta-oxidation gene expression by fatty acids in developing rats

Regulation of genes involved in fatty acid (FA) utilization in heart and Li ver of weanling rats was investigated in response to variations in dietary lipid content and to changes in intracellular FA homeostasis induced by eto moxir, a blocker of FA import into mitochondria. Northern-blot analyses wer e performed using cDNA probes specific for FA transport protein, a cell mem brane FA transporter; long-chain- and medium-chain acyl-CoA dehydrogenases, which catalyze the first step of mitochondrial FA beta -oxidation; and acy l-CoA oxidase, a peroxisomal FA beta -oxidation marker. High-fat feeding fr om postnatal d 21 to 28 resulted in a coordinate increase (58 to 136%) in m RNA. abundance of all genes in heart. In liver, diet-induced changes in mit ochondrial and peroxisomal beta -oxidation enzyme mRNAs (from 52 to 79%) oc curred with no change in FA transport protein gene expression. In both tiss ues, the increases in mRNA levels went together with parallel increases in enzyme activity. Changes in FA homeostasis resulting from etomoxir administ ration led to a marked stimulation (76 to 180%) in cardiac expression of al l genes together with parallel increases in enzyme activities. In the liver , in contrast, etomoxir stimulated the expression of acyl-CoA oxidase gene only. Feeding rats a low-fat diet containing 0.5% clofibrate, a ligand of p eroxisome proliferator-activated receptor alpha, resulted in similar induct ions of beta -oxidation enzyme genes in both tissues, whereas up-regulation of FA transport protein gene was restricted to heart. Altogether, these da ta suggest that changes in FA homeostasis in immature organs resulting eith er from high-fat diet or beta -oxidation blockade can efficiently be transd uced to the level of gene expression, resulting in tissue-specific adaptati ons in various FA-using enzymes and proteins.