Maternal plasma L-carnitine reduction during pregnancy is mainly attributed to OCTN2-mediated placental uptake and does not result in maternal hepatic fatty acid B-oxidation decline

Abstract

L-Carnitine (L-Car) plays a crucial role in fatty acid b-oxidation. However, the plasma L-Car concentration in women markedly declines during pregnancy, but the underlying mechanism and its consequences on maternal hepatic b-oxidation have not yet been clarified. Our results showed that the plasma L-Car level in mice at gestation day (GD) 18 was significantly lower than that in nonpregnant mice, and the mean fetal-to-maternal plasma L-Car ratio in GD 18 mice was 3.0. Carnitine/organic cation transporter 2 (OCTN2) was highly expressed in mouse and human placenta and upregulated as gestation proceeds in human placenta, whereas expressions of carnitine transporter (CT) 1, CT2, and amino acid transporter B0,+ were extremely low. Further study revealed that renal peroxisome proliferator–activated receptor a (PPARa) and OCTN2 were downregulated and the renal L-Car level was reduced, whereas the urinary excretion of L-Car was lower in late pregnant mice than in nonpregnant mice. Meanwhile, progesterone (pregnancy-related hormone) downregulated the expression of renal OCTN2 via PPARa-mediated pathway, and inhibited the activity of OCTN2, but estradiol, corticosterone, and cortisol did not. Unexpectedly, the maternal hepatic level of L-Car and b-hydroxybutyrate (an indicator of mitochondrial b-oxidation), and mRNA levels of several enzymes involved in fatty acid b-oxidation in GD 18 mice were higher than that in nonpregnant mice. In conclusion, OCTN2 mediated L-Car transfer across the placenta played a major role in maternal plasma L-Car reduction during pregnancy, which did not subsequently result in maternal hepatic fatty acid b-oxidation decrease.