Phosphatidylethanolamine N-Methyltransferase Knockout Modulates Metabolic Changes in Aging Mice

Area of Science:

• Biochemistry
• Metabolomics
• Aging Research

Background:

• Phospholipid metabolism, particularly phosphatidylcholine (PC) biosynthesis, is essential for biological functions and longevity.
• Phosphatidylethanolamine N-methyltransferase (PEMT) synthesizes PC, with its levels varying in organs during aging.
• The systemic role of PEMT in PC supply and its impact on aging energy metabolism remain unclear.

Purpose of the Study:

• To investigate the role of PEMT in aging-associated energy metabolism within key metabolic tissues.
• To determine how PEMT deficiency affects the metabolome in tissues involved in nutrient absorption, lipid storage, and energy consumption.

Main Methods:

• Utilized NMR-based metabolomics to analyze liver, plasma, intestine, adipose tissues (BAT and WAT), and skeletal muscle.
• Compared young and aged wild-type (WT) and PEMT knockout (KO) mice.
• Assessed tissue-specific and age-dependent metabolic changes.

Main Results:

• PEMT deficiency had tissue-specific and age-dependent effects on the metabolome.
• Brown adipose tissue (BAT) metabolome was dramatically altered in KO mice of all ages.
• Aging's impact on metabolome divergence was amplified in the liver, WAT, duodenum, and ileum of KO mice but lessened in skeletal muscle.

Conclusions:

• PEMT plays a critical, previously underappreciated role in regulating aging and energy metabolism.
• PEMT's influence on systemic PC supply and tissue-specific metabolic adaptations during aging is significant.
• Tissue-specific and age-dependent effects highlight PEMT's complex involvement in metabolic homeostasis.