Plasma Lipolysis and Changes in Plasma and Cerebrospinal Fluid Signaling Lipids Reveal Abnormal Lipid Metabolism in Chronic Migraine.
Plasma Lipolysis and Changes in Plasma and Cerebrospinal Fluid Signaling Lipids Reveal Abnormal Lipid Metabolism in Chronic Migraine.
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DOI：
10.3389/fnmol.2021.691733
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发表时间：
2021
影响因子：
4.8
通讯作者：
Fonteh AN
中科院分区：
文献类型：
--
作者：
Castor K;Dawlaty J;Arakaki X;Gross N;Woldeamanuel YW;Harrington MG;Cowan RP;Fonteh AN
脂类是能量的主要储存形式，也是炎症和疼痛信号分子的来源，但对其在慢性偏头痛(CM)病理中的重要性的了解尚不完全。我们的目标是确定血浆和脑脊液(CSF)脂代谢是否与CM的病理相关。我们从健康对照组(CT，n=10)或CM受试者(n=15)获取血浆和脑脊液，这些患者符合国际头痛协会的诊断标准。用气相色谱-质谱法测定未酯化脂肪酸(UFA)和酯化脂肪酸(EFAs)。用LC-MS/MS法测定甘油磷脂(GP)和鞘磷脂(SP)水平，用荧光底物法测定磷脂酶A2(PLA2)活性。未酯化脂肪酸水平在CM血浆中显著升高，而在脑脊液中无显著变化。CM血浆中5种饱和脂肪酸(SAFA)、8种单不饱和脂肪酸(MUFA)、5种ω-3多不饱和脂肪酸(PUFA)和5种ω-6多不饱和脂肪酸(PUFA)的非酯化水平较高。在CM血浆中，3个SAFA、8个MUFA、5个ω-3 PUFA和3个ω-6 PUFA的酯化水平较高。代表D5D的C20：4n-6/Homo-γ-C20：3n-6比值和延伸率分别在酯化和未酯化CM血浆中较低。在脑脊液中，CM的酯化D5D指数较低。在PLA2活性相近的情况下，CM组的血浆UFA/EFA比值较高。在所有检测到的血浆GP/SP中，只有神经酰胺水平在CM组(0.26±0.07%)低于CT组(0.48±0.06%)(p=0.0003)。CM-CSF中血小板活化因子(PAF)的GP/SP比例明显降低。血浆和脑脊液的脂质变化与CM的脂代谢异常相一致。由于血浆不饱和脂肪酸与饮食或脂肪组织水平相对应，较高的血浆脂肪酸和UFA/EFA比率提示CM患者脂肪分解增强。血浆和脑脊液脱饱和酶和延伸酶的差异提示CM的脂质代谢发生了改变。较低的血浆神经酰胺水平意味着从头合成减少或鞘磷脂水解率降低。脑脊液PAF的变化提示CM患者脑脂信号通路的不同。总而言之，这项初步研究表明，CM的脂质代谢异常对应于能量平衡的改变。我们认为，控制血浆脂解、去饱和酶、延伸酶和脂质信号通路可能会缓解CM症状。
Lipids are a primary storage form of energy and the source of inflammatory and pain signaling molecules, yet knowledge of their importance in chronic migraine (CM) pathology is incomplete. We aim to determine if plasma and cerebrospinal fluid (CSF) lipid metabolism are associated with CM pathology. We obtained plasma and CSF from healthy controls (CT, n = 10) or CM subjects (n = 15) diagnosed using the International Headache Society criteria. We measured unesterified fatty acid (UFA) and esterified fatty acids (EFAs) using gas chromatography-mass spectrometry. Glycerophospholipids (GP) and sphingolipid (SP) levels were determined using LC-MS/MS, and phospholipase A2 (PLA2) activity was determined using fluorescent substrates. Unesterified fatty acid levels were significantly higher in CM plasma but not in CSF. Unesterified levels of five saturated fatty acids (SAFAs), eight monounsaturated fatty acids (MUFAs), five ω-3 polyunsaturated fatty acids (PUFAs), and five ω-6 PUFAs are higher in CM plasma. Esterified levels of three SAFAs, eight MUFAs, five ω-3 PUFAs, and three ω-6 PUFAs, are higher in CM plasma. The ratios C20:4n-6/homo-γ-C20:3n-6 representative of delta-5-desaturases (D5D) and the elongase ratio are lower in esterified and unesterified CM plasma, respectively. In the CSF, the esterified D5D index is lower in CM. While PLA2 activity was similar, the plasma UFA to EFA ratio is higher in CM. Of all plasma GP/SPs detected, only ceramide levels are lower (p = 0.0003) in CM (0.26 ± 0.07%) compared to CT (0.48 ± 0.06%). The GP/SP proportion of platelet-activating factor (PAF) is significantly lower in CM CSF. Plasma and CSF lipid changes are consistent with abnormal lipid metabolism in CM. Since plasma UFAs correspond to diet or adipose tissue levels, higher plasma fatty acids and UFA/EFA ratios suggest enhanced adipose lipolysis in CM. Differences in plasma and CSF desaturases and elongases suggest altered lipid metabolism in CM. A lower plasma ceramide level suggests reduced de novo synthesis or reduced sphingomyelin hydrolysis. Changes in CSF PAF suggest differences in brain lipid signaling pathways in CM. Together, this pilot study shows lipid metabolic abnormality in CM corresponding to altered energy homeostasis. We propose that controlling plasma lipolysis, desaturases, elongases, and lipid signaling pathways may relieve CM symptoms.
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影响因子：
5.3
作者：
Akerman, Simon;Holland, Philip R.;Goadsby, Peter J.
通讯作者：
Goadsby, Peter J.
影响因子：
2.7
作者：
Baugh, Simon D. P.;Pabba, Praveen K.;Lombardo, Victoria K.
通讯作者：
Lombardo, Victoria K.
影响因子：
4.4
作者：
Bernstein, Adam M.;Roizen, Michael F.;Martinez, Luis
通讯作者：
Martinez, Luis
DOI：
10.1016/j.bbrc.2005.07.181
发表时间：
2005-12-09
影响因子：
3.1
作者：
Arita, M;Clish, CB;Serhan, CN
通讯作者：
Serhan, CN
影响因子：
5.3
作者：
Choi, Sarah M.;Tucker, David F.;Birnbaum, Morris J.
通讯作者：
Birnbaum, Morris J.