TY - JOUR
T1 - Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice
AU - Zhou, Qishun
AU - Zhang, Fangrong
AU - Kerbl-Knapp, Jakob
AU - Korbelius, Melanie
AU - Kuentzel, Katharina Barbara
AU - Vujić, Nemanja
AU - Akhmetshina, Alena
AU - Hörl, Gerd
AU - Paar, Margret
AU - Steyrer, Ernst
AU - Kratky, Dagmar
AU - Madl, Tobias
PY - 2022/9/9
Y1 - 2022/9/9
N2 - 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.
AB - 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.
KW - Aging
KW - Animals
KW - Liver/metabolism
KW - Mice
KW - Mice, Knockout
KW - Phosphatidylcholines
KW - Phosphatidylethanolamine N-Methyltransferase/genetics
KW - Phospholipids/metabolism
U2 - 10.3390/biom12091270
DO - 10.3390/biom12091270
M3 - Article
C2 - 36139111
SN - 2218-273X
VL - 12
JO - Biomolecules
JF - Biomolecules
IS - 9
M1 - 1270
ER -
