TY - JOUR T1 - Maternal Plasma <span class="sc">l</span>-Carnitine Reduction During Pregnancy Is Mainly Attributed to OCTN2-Mediated Placental Uptake and Does Not Result in Maternal Hepatic Fatty Acid <em>β</em>-Oxidation Decline JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 582 LP - 591 DO - 10.1124/dmd.119.086439 VL - 47 IS - 6 AU - Mengru Bai AU - Qingquan Zeng AU - Yingchun Chen AU - Mingyang Chen AU - Ping Li AU - Zhiyuan Ma AU - Dongli Sun AU - Hui Zhou AU - Caihong Zheng AU - Su Zeng AU - Huidi Jiang Y1 - 2019/06/01 UR - http://dmd.aspetjournals.org/content/47/6/582.abstract N2 - l-Carnitine (l-Car) plays a crucial role in fatty acid β-oxidation. However, the plasma l-Car concentration in women markedly declines during pregnancy, but the underlying mechanism and its consequences on maternal hepatic β-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 α (PPARα) 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 PPARα-mediated pathway, and inhibited the activity of OCTN2, but estradiol, corticosterone, and cortisol did not. Unexpectedly, the maternal hepatic level of l-Car and β-hydroxybutyrate (an indicator of mitochondrial β-oxidation), and mRNA levels of several enzymes involved in fatty acid β-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 β-oxidation decrease. ER -