AUTHOR=Yong Hannah E. J. , Watkins Oliver C. , Mah Tania K. L. , Cracknell-Hazra Victoria K. B. , Pillai Reshma Appukuttan , Selvam Preben , Islam Mohammad O. , Sharma Neha , Cazenave-Gassiot Amaury , Bendt Anne K. , Wenk Markus R. , Godfrey Keith M. , Lewis Rohan M. , Chan Shiao-Yng 

TITLE=Increasing maternal age associates with lower placental CPT1B mRNA expression and acylcarnitines, particularly in overweight women

JOURNAL=Frontiers in Physiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1166827

DOI=10.3389/fphys.2023.1166827

ISSN=1664-042X

ABSTRACT=<p>Older pregnant women have increased risks of complications including gestational diabetes and stillbirth. Carnitine palmitoyl transferase (CPT) expression declines with age in several tissues and is linked with poorer metabolic health. Mitochondrial CPTs catalyze acylcarnitine synthesis, which facilitates fatty acid oxidization as fuel. We hypothesized that the placenta, containing maternally-inherited mitochondria, shows an age-related CPT decline that lowers placental acylcarnitine synthesis, increasing vulnerability to pregnancy complications. We assessed <italic>CPT1A</italic>, <italic>CPT1B</italic>, <italic>CPT1C</italic> and <italic>CPT2</italic> mRNA expression by qPCR in 77 placentas and quantified 10 medium and long-chain acylcarnitines by LC-MS/MS in a subset of 50 placentas. Older maternal age associated with lower expression of placental <italic>CPT1B</italic>, but not <italic>CPT1A</italic>, <italic>CPT1C</italic> or <italic>CPT2</italic>. <italic>CPT1B</italic> expression positively associated with eight acylcarnitines and <italic>CPT1C</italic> with three acylcarnitines, <italic>CPT1A</italic> negatively associated with nine acylcarnitines, while <italic>CPT2</italic> did not associate with any acylcarnitine. Older maternal age associated with reductions in five acylcarnitines, only in those with BMI≥ 25 kg/m<sup>2</sup>, and not after adjusting for <italic>CPT1B</italic> expression. Our findings suggest that <italic>CPT1B</italic> is the main transferase for placental long-chain acylcarnitine synthesis, and age-related <italic>CPT1B</italic> decline may underlie decreased placental metabolic flexibility, potentially contributing to pregnancy complications in older women, particularly if they are overweight.</p>