Watkins, S M, et al., Phosphatidylethanolamine-N-Methyltransferase Activity and Dietary Choline Regulate Liver-Plasma Lipid Flux and Essential Fatty Acid Metabolism in Mice. J Nutr, 2003. 133(11): 3386-91.
Metabolon results led to:
- Revealed that PEMT activity has a much broader physiological function than previously appreciated
- Insight into how seemingly straight-forward nutritional interventions may have far more widespread effects
Key metabolomic observations:
- Plasma PC, TG and CE levels were not effected in PEMT KO animals with supplementation of choline
- Distinctions in essential fatty acid composition (AA and DHA) in liver and plasma PC in PEMT KO
Phosphatidylcholine (PC) is the most abundant phospholipid in cells and can be maintained by 2 pathways including the PEMT pathway. PEMT activity was thought to provide a compensatory route for phosphatidylcholine synthesis during periods of choline deficiency. To explore this possibility in more detail PEMT KO and WT mice fed choline deficient and choline supplemented diets were profiled for to characterize the full effects of PEMT on lipid metabolism. Choline supplementation rescued hepatic PC and TAG concentrations but could not restore plasma TAG concentrations. Further, AA and DHA were depleted from PC in the PEMT knockout independent of choline status. Thus Lipomics identified a key role for PEMT in both lipoprotein synthesis/metabolism and in the incorporation of essential fatty acids into key distribution pools. Further, by identifying these subtle distinctions, upon supplementation with choline, it offers insight into the likelihood that any nutritional intervention is likely to be far more complex than can be anticipated in theory.