PEMT-mediated phospholipid imbalance promotes age-associated metabolic dysfunction-associated steatotic liver disease progression
Data files
Nov 22, 2025 version files 81.72 KB
-
Lipidomics_data1121.xlsx
79.34 KB
-
README.md
2.38 KB
Abstract
Metabolically-dysfunction-associated steatotic liver disease [MASLD; previously known as nonalcoholic fatty liver disease (NAFLD)] is a prevalent chronic liver disorder strongly associated with aging, yet the mechanisms underlying age-related hepatic lipid dysregulation remain incompletely defined. This study investigates how aging alters hepatic phospholipid metabolism and the contribution of phosphatidylethanolamine N-methyltransferase (PEMT) to MASLD progression. Here, lipid accumulation was characterized in the livers of 2-, 6-, 12-, 18-, and 24-month-old mice, revealing age-dependent increases in hepatic triglyceride (TG), total cholesterol (TC), and lipid droplet formation. Lipidomic analysis revealed a marked imbalance in phospholipid composition, characterized by increased phosphatidylcholine (PC) and decreased phosphatidylethanolamine (PE), resulting in a 2.5-fold increase in the PC/PE ratio in 24-month-old mice compared to 6-month-old controls. Mechanistically, PEMT, a key enzyme regulating PC and PE metabolism, exhibited significantly increased expression (~2.4-fold at the protein level) in aged livers, suggesting a pivotal role in driving the observed phospholipid imbalance in vitro. PEMT inhibition significantly attenuated lipid droplet accumulation by ~30% and reduced intracellular TG levels by ~20% in D-galactose-induced senescent AML12 hepatocytes under lipid stress, compared to non-silenced senescent controls. These findings suggest that aging-driven PEMT [JH1] overexpression promotes phospholipid remodeling and hepatic lipid accumulation. By leveraging a natural aging mouse model, our study provides the first evidence linking PEMT activity to age-associated phospholipid dyshomeostasis, revealing a previously unknown mechanistic axis distinct from diet-induced MASLD and offering new therapeutic insights.
Dataset DOI: 10.5061/dryad.7d7wm386j
Description of the data and file structure
This dataset contains quantitative lipidomics profiling data derived from liver tissues of C57BL/6J mice. The experimental objective was to investigate age-associated alterations in the hepatic lipidome and to elucidate the role of PEMT-mediated phospholipid imbalance in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Liver samples were collected from two specific age groups: young mice (6 months old, denoted as 6M) and aged mice (24 months old, denoted as 24M). Total lipids were extracted from the liver tissues and analyzed using liquid chromatography-mass spectrometry (LC-MS). The provided data includes the identification and quantification (in nmol/g) of various lipid species, highlighting significant differences in lipid composition between young and aged livers.
Files and variables
File: scheme.tiff
Description: Schematic representation of the proposed mechanism. This figure illustrates how PEMT-mediated phospholipid imbalance acts as a driver for the progression of age-associated metabolic dysfunction-associated steatotic liver disease (MASLD). It summarizes the key metabolic alterations and signaling pathways identified in the study, highlighting the difference between young and aged liver phenotypes.
File: Lipidomics_data1121.xlsx
Description:
Variables
- NO: Row index number.
- lipid name: The specific identification of the lipid species.
- Ontology: The chemical classification or category of the lipid.
- 6M-M-[Number] (nmol/g): Quantitative lipid concentration in liver tissue from 6-month-old male mice. Unit: nanomoles per gram (nmol/g).
- 24M-M-[Number] (nmol/g): Quantitative lipid concentration in liver tissue from 24-month-old male mice. Unit: nanomoles per gram (nmol/g).
- Specialized abbreviations：6M: 6 months old (Age). 24M: 24 months old (Age). M: Male (Sex). nmol/g: Nanomoles per gram (unit of measurement).
No specialized code or scripts were used for the generation of this specific data file; the values are derived from LC-MS quantitative analysis.