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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\u201310 weeks) and old (91\u2013132 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.<\/jats:p>","DOI":"10.3390\/biom12091270","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T20:52:25Z","timestamp":1663015945000},"page":"1270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6181-0638","authenticated-orcid":false,"given":"Qishun","family":"Zhou","sequence":"first","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-2902","authenticated-orcid":false,"given":"Fangrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"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"},{"name":"Key Laboratory of Gastrointestinal Cancer, Fujian Medical University, Ministry of Education, Fuzhou 350122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Kerbl-Knapp","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-9436","authenticated-orcid":false,"given":"Melanie","family":"Korbelius","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-5466","authenticated-orcid":false,"given":"Katharina Barbara","family":"Kuentzel","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2977-7799","authenticated-orcid":false,"given":"Nemanja","family":"Vuji\u0107","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Akhmetshina","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0884-0851","authenticated-orcid":false,"given":"Gerd","family":"H\u00f6rl","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5494-8890","authenticated-orcid":false,"given":"Margret","family":"Paar","sequence":"additional","affiliation":[{"name":"Otto-Loewi Research Center, Division of Medicinal Chemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-5581","authenticated-orcid":false,"given":"Ernst","family":"Steyrer","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1357-7573","authenticated-orcid":false,"given":"Dagmar","family":"Kratky","sequence":"additional","affiliation":[{"name":"Gottfried Schatz Research Center for Cell Signaling, 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