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Developmental changes in carnitine octanoyltransferase gene expression in intestine and liver of suckling rats
A Miliar1, D Serra, R Casaroli
1Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain.
Insights
Carnitine octanoyltransferase (COT) expression in rat intestines and liver changes during development. Its regulation appears transcriptional, influenced by maternal milk and weaning age, impacting fatty acid metabolism.
Area of Science:
- Biochemistry
- Molecular Biology
- Developmental Biology
Background:
- Carnitine octanoyltransferase (COT) is crucial for transporting fatty acyl-CoAs between peroxisomes and mitochondria.
- Understanding COT's developmental expression is key to elucidating fatty acid metabolism regulation in early life.
Purpose of the Study:
- To investigate the developmental expression pattern of Carnitine octanoyltransferase (COT) in the intestinal mucosa and liver of suckling rats.
- To explore the transcriptional regulation of COT during postnatal development.
- To assess the influence of maternal milk and weaning on intestinal COT expression.
Main Methods:
- Quantitative analysis of COT mRNA and pre-mRNA levels in rat intestine and liver at various postnatal ages.
- Comparison of developmental expression profiles with related metabolic enzymes.
Main Results:
- Intestinal COT mRNA levels rise rapidly post-birth, plateauing around day 15, then declining to adult levels by weaning.
- Hepatic COT mRNA peaks at day 3, remains stable until day 9, and subsequently decreases.
- Developmental patterns of mRNA and pre-mRNA suggest transcriptional control; maternal milk and weaning age influence intestinal COT expression.
Conclusions:
- COT expression in rat intestine and liver follows distinct developmental trajectories, primarily regulated at the transcriptional level.
- The expression patterns suggest a coordinated regulation of peroxisomal and mitochondrial fatty acid oxidation, potentially involving shared transcription factors.
- Maternal diet and weaning practices significantly impact the developmental expression of COT in the intestine.
Abstract:
Carnitine octanoyltransferase (COT), which facilitates the transport of shortened fatty acyl-CoAs from peroxisomes to mitochondria, is expressed in the intestinal mucosa of suckling rats; its mRNA levels increase rapidly after birth, remain steady until day 15, and decrease until weaning, when basal, adult values are established, which remain unchanged thereafter. The process seems to be controlled at the transcriptional level since the developmental pattern of mRNA coincides with that of pre-mRNA values. Dam's milk may influence the intestinal expression of COT, since mRNA levels at birth are low and increase after the first lactation. Moreover, mRNA levels decrease in rats weaned on day 18 or 21. COT is also expressed in the liver of suckling rats. Hepatic COT mRNA is maximal at day 3, remains constant until day 9, and decreases thereafter; this pattern is also similar to that of pre-mRNA values. The profile of expression of COT in intestine and liver strongly resembles that of mitochondrial 3-hydroxy 3-methylglutaryl-coenzyme A synthase and carnitine palmitoyltransferase I, suggesting that analogous transcription factors modulate ketogenesis and mitochondrial and peroxisomal fatty acid oxidation.