2025/05/13 by Tamara Carnac · 1 voice
Medicine · #Fibromyalgia and Chronic Fatigue Syndrome Research
paper · pdf · doi:10.20944/preprints202409.1467.v3
openalex publication_date 2025/05/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Myalgic Encephalomyelitis (ME), sometimes known as Chronic Fatigue Syndrome (CFS), is a complex illness marked by fatigue, post-exertional malaise, cognitive dysfunction, autonomic instability, and immune abnormalities. This paper proposes a unifying hypothesis centred on dysfunction of lecithin–cholesterol acyltransferase (LCAT) and deficiency of phosphatidylcholine (PC), leading to altered membrane lipid composition, excess arachidonic acid release, and chronic inflammation. These changes may promote dysregulated production of prostaglandins and leukotrienes, imbalance in PPAR-γ activity, and disruptions in sex hormone metabolism, potentially contributing to conditions like polycystic ovary syndrome (PCOS), endometriosis and mast cell activation syndrome (MCAS). We propose that different combinations of LCAT dysfunction and PC deficiency result in distinct physiological subtypes. These include a neuronal insulin-hypersensitive subtype with reduced norepinephrine transporter (NET) expression and high extracellular norepinephrine; a high membrane arachidonic acid subtype with preserved PC but increased NET expression and neuronal insulin resistance; and a third group characterised by both elevated norepinephrine and downregulated β₂-adrenergic receptors. Each subtype presents with a different pattern of autonomic, metabolic, and immune dysregulation. Additional variation may arise from differences in acetylcholine synthesis, norepinephrine production capacity, and feedback mechanisms within the adrenergic system. This framework helps explain the heterogeneity of ME and offers a biologically coherent basis for further investigation into its pathophysiology.