Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Phosphatidylethanolamine N-methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

Qishun Zhou
ORCID logo ,
Fangrong Zhang
ORCID logo ,
Jakob Kerbl-Knapp
,
Melanie Korbelius
ORCID logo ,
Katharina B. Kuentzel
ORCID logo ,
Nemanja Vujic
ORCID logo ,
Alena Akhmetshina
,
Gerd Hörl
ORCID logo ,
Margret Paar
ORCID logo ,
Ernst Steyrer
ORCID logo ,
Dagmar Kratky
ORCID logo ,
Tobias Madl
* ORCID logo
Version 1 : Received: 5 August 2022 / Approved: 8 August 2022 / Online: 8 August 2022 (13:36:04 CEST)

A peer-reviewed article of this Preprint also exists.

Zhou, Q.; Zhang, F.; Kerbl-Knapp, J.; Korbelius, M.; Kuentzel, K.B.; Vujić, N.; Akhmetshina, A.; Hörl, G.; Paar, M.; Steyrer, E.; Kratky, D.; Madl, T. Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice. Biomolecules 2022, 12, 1270. Zhou, Q.; Zhang, F.; Kerbl-Knapp, J.; Korbelius, M.; Kuentzel, K.B.; Vujić, N.; Akhmetshina, A.; Hörl, G.; Paar, M.; Steyrer, E.; Kratky, D.; Madl, T. Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice. Biomolecules 2022, 12, 1270.

Abstract

Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated to longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as brain and kidney 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 liver, plasma, intestine (duodenum, jejunum, ileum), brown/white adipose tissues (BAT, WAT), and skeletal muscle of young (9–10 weeks) and old (96–104 weeks) wild-type (WT) and PEMT knockout (KO) mice. We found that the effect of PEMT-knockout was tissue-specific and age-dependent. 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 WT mice, whereas the metabolome of jejunum was only slightly affected. As for aging, the absence of PEMT increased the divergence of metabolome during aging of liver, WAT, duodenum and ileum and decreased the impact on skeletal muscle. Overall, our results suggest that PEMT plays a previously unexplored critical role in both aging and energy metabolism.

Keywords

metabolomics; NMR; PEMT; knockout; aging; mice; liver; intestine; white/brown adipose tissue

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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