Targeted fatty acid metabolomics to discover Parkinson's disease associated metabolic alteration

Abstract

The pathogenesis of Parkinson's disease (PD) remains to be elucidated, and the metabolomics analysis has the potential to identify metabolic profiles that are involved in PD pathogenesis. Here we applied a target metabolomics approach to measure the plasma levels of 158 fatty acid metabolites in a discovery cohort including 42 PD patients and 54 health volunteers, and found two upregulated (arachidonic acid and 13-hydroxy-octadecatrienoic acid) and eleven down-regulated (docosahexaenoic acid, lyso-platelet-activating factor, 12-hydroxy-eicosatetraenoic acid, dihydroxy-eicosatrienoic acids, dihidroxy-octadecenoic acids, 17,18-dihydroxyeicosatetraenoic acid, and hydroperoxy-octadecadienoic acids) metabolites as primary candidate marker of PD. A support vector machine algorithm with primary candidate marker was used in an independent validation cohort to identify PD. Arachidonic acid and 13-hydroxy-octadecatrienoic acid were evaluated as an effective tool in that area under the receiver operating characteristic curve reached 0.995 and 0.912 in the validation set for diagnosing PD from healthy volunteers.Besides, the sensitivity and specificity of arachidonic acid as diagnostic factor of PD in validation set were 100% and 94.10%. Similarly, the sensitivity and specificity of 13-hydroxy-octadecatrienoic acid were 100% and 82.40% for identifying PD. This target fatty acid metabolomics demonstrated a series of plasma fatty acid metabolite as PD candidate marker with high efficiency and provided insights into the understanding of PD metabolic regulation.

Insulin resistance compromises midbrain organoid neural activity and metabolic efficiency predisposing to Parkinson’s disease pathology

“…Arachidonic acid is one the most abundant fatty acids in the brain and it has been associated with the prevention of α-Synuclein protein aggregation (40) and neuroprotection in animal models (41). Moreover, it has been reported as a potential biomarker in PD (42), suggesting its relevance in disease progression. Additionally, one of the most abundant cell membrane phospholipids – phosphatidylcholines were found to be significantly reduced in IR organoids, suggesting insulin resistance effect on cellular membrane integrity.…”

Rhynchophylline alleviates neuroinflammation and regulates metabolic disorders in a mouse model of Parkinson's disease

“…7 Serum metabolomics can reveal changes in metabolic pathways associated with PD progression. [30][31][32] In this study, a non-targeted serum metabolomics approach was employed to elucidate the potential pathways of RIN against PD. MPTP-induced and RIN-targeted differential metabolic pathways were identified by functional enrichment analysis.…”

“…This finding is supported by a recent study in which 12-HETE and 17,18-DiHETE were significantly reduced in the serum of PD patients, and their abnormal changes might be the inducing factors of PD. 32 12-HETE has been demonstrated to exert an anti-apoptotic effect by upregulating the expression of B-cell lymphoma-2 (Bcl-2) and inhibiting the activity of caspase-3. 33 AA can also be catalyzed by COXs to produce various prostaglandins, which can regulate inflammation, immunity, 34 and capillary permeability.…”

Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling

“…In four studies, decreased levels of oleic acid in the blood of PD patients [20,23,21,24] may reflect the reduced neuroprotective effects in PD patients. Increased levels of polyunsaturated fatty acids [25,26,27,28,29,20,30], especially arachidonic acid [20,27,28,24,29], were identified in the plasma and CSF of PD patients. The weaker C-H bond at the bis-allylic position makes these fatty acids vulnerable to lipid peroxidation, and newly generated deleterious lipid peroxidation end products further influence cellular functions by altering membrane structure and circulating lipids [31].…”