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Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

Zhou, Qishun ; Zhang, Fangrong ; Kerbl-Knapp, Jakob ; Korbelius, Melanie ; Kuentzel, Katharina Barbara LU orcid ; Vujić, Nemanja ; Akhmetshina, Alena ; Hörl, Gerd ; Paar, Margret and Steyrer, Ernst , et al. (2022) In Biomolecules 12(9).
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
keywords
Aging, Animals, Liver/metabolism, Mice, Mice, Knockout, Phosphatidylcholines, Phosphatidylethanolamine N-Methyltransferase/genetics, Phospholipids/metabolism
in
Biomolecules
volume
12
issue
9
article number
1270
publisher
MDPI AG
external identifiers
  • scopus:85138753301
  • pmid:36139111
ISSN
2218-273X
DOI
10.3390/biom12091270
language
English
LU publication?
no
id
00e8688e-0f8f-4f3b-aecf-732b713fade8
date added to LUP
2022-10-10 16:30:46
date last changed
2024-04-18 09:47:23
@article{00e8688e-0f8f-4f3b-aecf-732b713fade8,
  abstract     = {{<p>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.</p>}},
  author       = {{Zhou, Qishun and Zhang, Fangrong and Kerbl-Knapp, Jakob and Korbelius, Melanie and Kuentzel, Katharina Barbara and Vujić, Nemanja and Akhmetshina, Alena and Hörl, Gerd and Paar, Margret and Steyrer, Ernst and Kratky, Dagmar and Madl, Tobias}},
  issn         = {{2218-273X}},
  keywords     = {{Aging; Animals; Liver/metabolism; Mice; Mice, Knockout; Phosphatidylcholines; Phosphatidylethanolamine N-Methyltransferase/genetics; Phospholipids/metabolism}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{9}},
  publisher    = {{MDPI AG}},
  series       = {{Biomolecules}},
  title        = {{Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice}},
  url          = {{http://dx.doi.org/10.3390/biom12091270}},
  doi          = {{10.3390/biom12091270}},
  volume       = {{12}},
  year         = {{2022}},
}