Journal
BIOMOLECULES
Volume 12, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/biom12091270
Keywords
metabolomics; NMR; PEMT; knockout; aging; mice; liver; intestine; white; brown adipose tissue
Categories
Funding
- Austrian Science Fund (FWF) [P28854, I3792, DOC-130, DK-MCD W1226]
- Austrian Research Promotion Agency (FFG) [864690, 870454]
- Integrative Metabolism Research Center Graz
- Austrian Infrastructure Program
- Styrian Government (Zukunftsfonds, doc.fund program)
- BioTechMed-Graz (flagship project)
- FWF [DK-MCD W1226, SFB F73, P32400, P30882, DOC 31]
- Province of Styria
- City of Graz [A27102000025]
- Startup Fund for High-level Talents of Fujian Medical University [XRCZX2021020]
- Natural Science Foundation of Fujian Province [2022J01660]
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This study investigates the impact of PEMT on aging-associated energy metabolism using metabolomics. The results show that the effect of PEMT knockout is tissue-specific and age-dependent. Additionally, the absence of PEMT increases the divergence of the metabolome during aging in the liver, adipose tissues, and intestines.
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.
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