Developmental Maturation and Segmental Distribution of Rat Small Intestinal L-Carnitine Uptake

Abstract

Oral L-carnitine supplementation is commonly used in sports nutrition and in medicine; however, there is controversy regarding the mechanisms that mediate intestinal L-carnitine transport. We have previously reported that the Na(+)/L-carnitine transporter OCTN2 is present in the small intestinal apical membrane. Herein we aimed to find out if this step of intestinal L-carnitine absorption is ontogenically regulated, and if so, to determine the molecular mechanism(s) involved. L-[(3)H]-Carnitine uptake was measured in the jejunum and ileum of fetuses (E17 and E21), newborn (1 day-old), suckling (15 day-old), weaning (1 month-old) and adult (2 and 6 month-old) Wistar rats. Both, Na(+) -dependent and Na(+) -independent L-carnitine uptake rates, normalized to intestinal weight, significantly increased during the late gestation period, and then declined during the suckling period. After weaning, the rate of Na(+) -dependent L-carnitine uptake is no longer measurable. In E21- fetuses and newborn rats, L-carnitine uptake was higher in the ileum than in the jejunum. The decline in Na(+) -dependent L-carnitine uptake with maturation was mediated via a decrease in the V(max) of the uptake process with no change in its apparent K(m). Semi-quantitative RT-PCR assays showed that OCTN2 mRNA levels were significantly higher in E21-fetuses and newborn rats compared to suckling rats, which were in turn significantly higher than that in adult rats. Neither retardation of weaning nor L-carnitine supplementation prevented the down-regulation of Na(+)/L-carnitine transport activity. The results demonstrate for the first time that intestinal Na(+) -dependent L-carnitine uptake activity is under genetic regulation at the transcriptional level.

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

“…This pattern of mRNA expression parallels the decline in sodium-dependent uptake of L-carnitine with advancing age (García-Miranda et al, 2005).…”

“…Octn2 mRNA in the rat jejunum and ileum is expressed higher perinatally and decreases 1 day after birth through 6 months of age (García-Miranda et al, 2005). This pattern of mRNA expression parallels the decline in sodium-dependent uptake of L-carnitine with advancing age (García-Miranda et al, 2005).…”

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

“…In our study expression of small intestinal Octn2 and Octn3 did not change with postnatal development, while Octn1 expression increased significantly between PD4 to PD8 remaining relatively constant after PD8. A previous study, which examined the postnatal maturation of the intestinal uptake L-carnitine, noted that Na + -dependent and Na + -independent intestinal uptake of L-carnitine was high in late gestation and in the newborn and significantly decreased between PD1 and PD15 [32]. Furthermore, mRNA expression of Octn2 demonstrated only a 20 % decrease between PD1 and PD15 in the jejunum, while ileal expression demonstrated a 100 % decrease between these two postnatal age groups [32].…”

“…A previous study, which examined the postnatal maturation of the intestinal uptake L-carnitine, noted that Na + -dependent and Na + -independent intestinal uptake of L-carnitine was high in late gestation and in the newborn and significantly decreased between PD1 and PD15 [32]. Furthermore, mRNA expression of Octn2 demonstrated only a 20 % decrease between PD1 and PD15 in the jejunum, while ileal expression demonstrated a 100 % decrease between these two postnatal age groups [32]. In our study Octn2 mRNA expression was evaluated in the jejunum, and the constant expression of Octn2 and Octn3 is consistent with these findings.…”

Transport of butyryl-l-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB0,+

“…Carnitine is transported in the intestine by OCTN2, and the process is developmentally regulated (10,11,15,25), thus making carnitine and fatty acid oxidation highly relevant in normal gut function. There are several reports linking inhibition of fatty acid oxidation in the gut with inflammation (23,43,44); likewise, L-carnitine has also been shown to play a protective role in gut inflammation (7,18).…”