Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a...

Area of Science:

• Immunometabolism
• Cellular metabolism
• Systems biology

Background:

• Growing evidence suggests a metabolic shift in lymphoid cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients, with increased lipid demand.
• Previous studies screened B cell-derived lymphoblastoid cell lines (LCLs) from ME/CFS patients, observing elevated expression of genes involved in amino acid and fatty acid degradation.
• This study expands on prior work by integrating multi-omic data to further characterize metabolic alterations in ME/CFS.

Purpose of the Study:

• To comprehensively profile the metabolome and lipidome of lymphoblastoid cell lines (LCLs) from ME/CFS patients.
• To integrate metabolomic and lipidomic data with existing proteomic and transcriptomic data.
• To identify specific metabolic pathways and molecular players involved in ME/CFS pathogenesis.

Main Methods:

• Profiling of polar metabolomes and non-polar lipidomes in LCLs from 15 ME/CFS patients and 17 healthy controls.
• Integration of metabolomic and lipidomic data with previously generated proteomic and transcriptomic datasets.
• Utilized MetaboAnalyst for integrated multi-omic analysis and BioPAN for lipidomic pathway analysis.

Main Results:

• No significantly altered individual features were detected in the polar metabolome; however, 15 dysregulated pathways were identified via integrated analysis.
• Significantly reduced levels of PC(O-38:4) were observed in ME/CFS LCLs, with elevated levels of triglycerides, diradylglycerolipids, and fatty acids.
• Integrated analysis revealed elevated phosphatidylserine synthase 1 (PTDSS1) and other concordantly altered gene products, alongside a tendency towards more saturated lipid content in ME/CFS LCLs.

Conclusions:

• ME/CFS patient-derived LCLs exhibit lipid accumulation, skewed lipid profiles, and altered metabolic enzyme activity (e.g., PTDSS1).
• These findings highlight potential immunometabolic dysregulations involving lipid abnormalities in ME/CFS.
• The results provide a foundation for future studies investigating specific immune cell populations and their effector functions in ME/CFS.