Phosphatidylethanolamine <i>N</i>-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice
Qishun Zhou,
Fangrong Zhang,
Jakob Kerbl-Knapp,
Melanie Korbelius,
Katharina Barbara Kuentzel,
Nemanja Vujić,
Alena Akhmetshina,
Gerd Hörl,
Margret Paar,
Ernst Steyrer,
Dagmar Kratky,
Tobias Madl
Affiliations
Qishun Zhou
Research Unit Integrative Structural Biology, Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, 8010 Graz, Austria
Fangrong Zhang
Research Unit Integrative Structural Biology, Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, 8010 Graz, Austria
Jakob Kerbl-Knapp
Research Unit Integrative Structural Biology, Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, 8010 Graz, Austria
Melanie Korbelius
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Katharina Barbara Kuentzel
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Nemanja Vujić
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Alena Akhmetshina
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Gerd Hörl
Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria
Margret Paar
Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria
Ernst Steyrer
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Dagmar Kratky
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Tobias Madl
Research Unit Integrative Structural Biology, Division of Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, 8010 Graz, Austria
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.
