Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

Abstract

Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated with longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as the brain and kidneys during aging. However, the role of PEMT for systemic PC supply is not fully understood. To address how PEMT affects aging-associated energy metabolism in tissues responsible for nutrient absorption, lipid storage, and energy consumption, we employed NMR-based metabolomics to study the liver, plasma, intestine (duodenum, jejunum, and ileum), brown/white adipose tissues (BAT and WAT), and skeletal muscle of young (9–10 weeks) and old (91–132 weeks) wild-type (WT) and PEMT knockout (KO) mice. We found that the effect of PEMT-knockout was tissue-specific and age-dependent. A deficiency of PEMT affected the metabolome of all tissues examined, among which the metabolome of BAT from both young and aged KO mice was dramatically changed in comparison to the WT mice, whereas the metabolome of the jejunum was only slightly affected. As for aging, the absence of PEMT increased the divergence of the metabolome during the aging of the liver, WAT, duodenum, and ileum and decreased the impact on skeletal muscle. Overall, our results suggest that PEMT plays a previously underexplored, critical role in both aging and energy metabolism.

The Association between the Plasma Phospholipid Profile and Insulin Resistance: A Population-Based Cross-Section Study from the China Adult Chronic Disease and Nutrition Surveillance

“…In fact, PC could be synthesized via three different pathways: the de novo synthesis Kennedy pathway, the Lands’ cycle, as mentioned above, and the PEMT pathway [ 26 ]. According to animal-level experiment studies, the knockout of PEMT, the critical enzyme for the conversion of PE to PC, resulted in a significant decrease in hepatic PC:PE ratio and insulin resistance [ 10 , 27 , 28 ], suggesting that the changes in PC-PE balance could affect the insulin sensitivity in vivo. And a deficiency of muscle CEPT1, the terminal enzyme for de novo synthesis of PC in the Kennedy pathway, resulted in a significant reduction of two diacyl-PEs and an significant increase in three diacyl-PCs containing docosahexaenoic acyl (DHA) or arachidonic acyl (AA) moieties in muscle endoplasmic reticulum, and improved insulin sensitivity in high-fat-diet mice [ 9 , 29 ].…”

Decoding Organelle Interactions: Unveiling Molecular Mechanisms and Disease Therapies

“…Excessive Ca 2+ activates calpains that cleave autophagy‐related proteins, such as ATG5, thus inhibiting mitochondrial autophagy. [ 124 ] In addition, this complex may regulate atrial remodeling by regulating calcium interaction between the ER and mitochondria.…”

Phosphatidylethanolamine N-methyltransferase: from Functions to Diseases

“…Evidence indicates that dysregulated lipid metabolism contributes to aging via various mechanisms [113][114][115]. Zhou et al [116] demonstrated that the absence of PEMT increases the divergence of the metabolome during the aging process of the gastrointestinal tract and liver. The vulnerability of the brain increases rapidly with age, and the lipid fatty acid composition of the brain membrane changes with age [117].…”