Abstract
Regulation of genes involved in fatty acid (FA) utilization in heart and liver of weanling rats was investigated in response to variations in dietary lipid content and to changes in intracellular FA homeostasis induced by etomoxir, a blocker of FA import into mitochondria. Northern-blot analyses were performed using cDNA probes specific for FA transport protein, a cell membrane FA transporter; long-chain- and medium-chain acyl-CoA dehydrogenases, which catalyze the first step of mitochondrial FA β-oxidation; and acyl-CoA oxidase, a peroxisomal FA β-oxidation marker. High-fat feeding from postnatal d 21 to 28 resulted in a coordinate increase (58 to 136%) in mRNA abundance of all genes in heart. In liver, diet-induced changes in mitochondrial and peroxisomal β-oxidation enzyme mRNAs (from 52 to 79%) occurred with no change in FA transport protein gene expression. In both tissues, the increases in mRNA levels went together with parallel increases in enzyme activity. Changes in FA homeostasis resulting from etomoxir administration led to a marked stimulation (76 to 180%) in cardiac expression of all 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 peroxisome proliferator-activated receptor α, resulted in similar inductions of β-oxidation enzyme genes in both tissues, whereas up-regulation of FA transport protein gene was restricted to heart. Altogether, these data suggest that changes in FA homeostasis in immature organs resulting either from high-fat diet or β-oxidation blockade can efficiently be transduced to the level of gene expression, resulting in tissue-specific adaptations in various FA-using enzymes and proteins.
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Abbreviations
- FATP:
-
fatty acid transport protein
- LCAD:
-
long-chain acyl-CoA dehydrogenase
- MCAD:
-
medium-chain acyl-CoA dehydrogenase
- ACO:
-
acyl-CoA oxidase
- PPARα:
-
peroxisome proliferator-activated receptor α
- CPT-1:
-
carnitine palmitoyltransferase I
- NEFA:
-
nonesterified fatty acid
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Acknowledgements
The authors thank Drs. A. Strauss and D.P. Kelly for providing us with the rat LCAD and MCAD cDNAs, respectively. We also thank Dr. J.E. Schaffer for the gift of the mouse FATP cDNA.
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Ouali, F., Djouadi, F., Merlet-Bénichou, C. et al. Regulation of Fatty Acid Transport Protein and Mitochondrial and Peroxisomal β-Oxidation Gene Expression by Fatty Acids in Developing Rats. Pediatr Res 48, 691–696 (2000). https://doi.org/10.1203/00006450-200011000-00023
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DOI: https://doi.org/10.1203/00006450-200011000-00023
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