Interictal, circulating sphingolipids in women with episodic migraine

Abstract

Objective: To evaluate interictal, circulating sphingolipids in women migraineurs.Methods: In the fasting state, serum samples were obtained pain-free from 88 women with episodic migraine (EM; n 5 52) and from controls (n 5 36). Sphingolipids were detected and quantified by high-performance liquid chromatography coupled with tandem mass spectrometry using multiple reaction monitoring. Multivariate logistic regression was used to examine the association between serum sphingolipids and EM odds. A recursive partitioning decision tree based on the serum concentrations of 10 sphingolipids was used to determine the presence or absence of EM in a subset of participants.Results: Total ceramide (EM 6,502.9 ng/mL vs controls 10,518.5 ng/mL; p , 0.0001) and dihydroceramide (EM 39.3 ng/mL vs controls 63.1 ng/mL; p , 0.0001) levels were decreased in those with EM as compared with controls. Using multivariate logistic regression, each SD increase in total ceramide (odds ratio [OR] 0.07; 95% confidence interval [CI]: 0.02, 0.22; p , 0.001) and total dihydroceramide (OR 0.05; 95% CI: 0.01, 0.21; p , 0.001) levels was associated with more than 92% reduced odds of migraine. Although crude sphingomyelin levels were not different in EM compared with controls, after adjustments, every SD increase in the sphingomyelin species C18:0 (OR 4.28; 95% CI: 1.87, 9.81; p 5 0.001) and C18:1 (OR 2.93; 95% CI: 1.55, 5.54; p 5 0.001) was associated with an increased odds of migraine. Recursive portioning models correctly classified 14 of 14 randomly selected participants as EM or control. Conclusion:These results suggest that sphingolipid metabolism is altered in women with EM and that serum sphingolipid panels may have potential to differentiate EM presence or absence. Classification of evidence:This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine. Neurology ® 2015;85:1214-1223 GLOSSARY BMI 5 body mass index; C1P 5 ceramide-1-phosphate; CI 5 confidence interval; DHC 5 dihydroceramide; DHSM 5 dihydrosphingomyelin; DSM-IV 5 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition); EM 5 episodic migraine; HIT-6 5 Headache Impact Test-6; LacCer 5 lactosylceramide; MHC 5 monohexosylceramide; OPLS-DA 5 orthogonal partial least squares discriminant analysis; OR 5 odds ratio; PHQ-9 5 Patient Health Questionnaire-9; S1P 5 sphingosine-1-phosphate; SM 5 sphingomyelin.Although the full pathophysiology of migraine is not known, current theories suggest that migraine is largely an inherited brain disorder associated with a sterile, neurogenic inflammation and alterations in neuronal excitability and the cerebrovasculature.1,2 Several lines of evidence also indicate that migraineurs have a greater risk of stroke and disorders related to lipid metabolism including hypercholesterolemia, impaired insulin sensitivity, and obesity. [3][4][5][6] Sphingolipids (e.g., sphingomyelins, ceramides) are a group of bioactive lipids that are critical components of m...

Sex‐specific perturbation of complex lipids in response to medium‐chain fatty acids in very long‐chain acyl‐CoA dehydrogenase deficiency

“…However, VLCAD ablation led to a striking increment in female mice. These data are indicative of a more generalized inflammatory response , which correlates well with our previous observation on the development of a severe metabolic syndrome in VLCAD −/− female mice on MCT . Indeed, behind their structural role and their several cellular functions , these lipids are the main components of microdomains that allow membrane compartmentalization of transporter and receptors and act directly as a messenger in the inflammatory response .…”

Different Lipid Signature in Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

“…Lipotoxicity due to accumulated long-chain acylcarnitines has been proposed as a mechanism of chronic and subclinical inflammation associated with lc-FAOD [ 52 ]. Indeed, studies on VLCAD −/− mice identified an inflammation as defined by an increase in lipid classes involved in inflammatory response signaling cascades [ 12 , 26 , 53 , 54 , 55 ]. It is also important to highlight the altered composition of LP that clearly reflects the incorporation of the accumulated fatty acids.…”

Untargeted Metabolomics Analysis using LC-MSQTOF for Metabolite Profile Comparison between Patients with Myofascial Pain of Upper Trapezius Muscle versus Controls

“…Total ceramides were also found to be lower in individuals with episodic migraine compared with controls, whereas sphingomyelin species were higher. 26 In patients with nociceptive and neuropathic pain, sphingomyelin and lipid metabolites were altered. 27,28 The decrease in lysoSM could be due to the conversion of sphingomyelin to ceramides, including this study.…”