代谢组学在代谢性脑血管病中的应用研究

doi:10.3969/j.issn.1673-5765.2024.02.004

摘要/Abstract

摘要： 脑血管病是全球范围内导致人类死亡和残疾的主要原因，其中很高比例与代谢紊乱相关。代谢性脑血管病是指由传统代谢危险因素和残余代谢危险因素导致的脑血管损害，以血管结构受损及功能障碍为主要病理生理学表现，干预代谢危险因素可有效改善预后的一种临床综合征。代谢组学是采用高通量组学技术对所有代谢物进行鉴定和定量的手段，是未来研究代谢性脑血管病的重要抓手。本文总结了代谢组学、脂质组学在代谢性心脑血管疾病方面的研究，旨在为代谢性脑血管病的代谢组学研究开展及其临床防治提供参考。

文章导读： 代谢组学、脂质组学可用于探索代谢产物在代谢性脑血管病中的作用及其受遗传和生活方式等因素的调节机制，有望为代谢性脑血管病的治疗策略提供新思路。

关键词: 代谢性脑血管病; 代谢组学; 脂质组学

Abstract: Cerebrovascular diseases are the leading cause of death and disability worldwide. A high proportion of cerebrovascular diseases is correlated with metabolism disorder. Cerebro-metabolic disease refers to a clinical syndrome with cerebrovascular injury caused by traditional metabolic risk factors and residual metabolic risk factors, vascular structural injury and dysfunction as the main pathophysiological manifestations, and intervention of metabolic risk factors can effectively improve the prognosis. Metabolomics is a scientific method that uses high-throughput omics technology to identify and quantify all metabolites, which is an important starting point for future research on cerebro-metabolic disease. This paper summarizes the studies of metabolomics and lipidomics in cerebro-metabolic disease and cardiometabolic disease, aiming to provide references for the development of metabolomics studies and clinical prevention and treatment of cerebro-metabolic disease.

Key words: Cerebro-metabolic disease; Metabolomics; Lipidomics

中图分类号:

钟文华, 薛婧, 许杰. 代谢组学在代谢性脑血管病中的应用研究[J]. 中国卒中杂志, 2024, 19(2): 145-149.

ZHONG Wenhua, XUE Jing, XU Jie. Application of Metabolomics in Cerebro-Metabolic Disease[J]. Chinese Journal of Stroke, 2024, 19(2): 145-149.

参考文献

[1] 许杰，王拥军. 代谢性脑血管病：概念、方法、挑战和未来方向[J]. 中国卒中杂志，2023，18（6）：617-627.
XU J，WANG Y J. Cerebro-metabolic disease：concept，method，challenge and future directions[J]. Chin J Stroke，2023，18（6）：617-627.
[2] IIDA M，HARADA S，TAKEBAYASHI T. Application of metabolomics to epidemiological studies of atherosclerosis and cardiovascular disease[J]. J Atheroscler Thromb，2019，26（9）：747-757.
[3] LIU M T，TANG L Y，LIU X，et al. An evidence-based review of related metabolites and metabolic network research on cerebral ischemia[J/OL]. Oxid Med Cell Longev，2016，2016：9162074[2023-11-01]. https://doi.org/10.1155/2016/9162074.
[4] MIETUS-SNYDER M，PERAK A M，CHENG S，et al. Next generation，modifiable cardiometabolic biomarkers：mitochondrial adaptation and metabolic resilience：a scientific statement from the American Heart Association[J]. Circulation，2023，148（22）：1827-1845.
[5] MCGARRAH R W，CROWN S B，ZHANG G F，et al. Cardiovascular metabolomics[J]. Circ Res，2018，122（9）：1238-1258.
[6] NELSON S E，AMENT Z，WOLCOTT Z，et al. Succinate links atrial dysfunction and cardioembolic stroke[J/OL]. Neurology，2019，92（8）：e802-e810[2023-11-01]. https://doi.org/10.1212/WNL.0000000000006957.
[7] YONESHIRO T，KATAOKA N，WALEJKO J M，et al. Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever[J/OL]. Elife，2021，10：e66865[2023-11-01].
https://doi.org/10.7554/eLife.66865.
[8] BLAIR M C，NEINAST M D，ARANY Z. Whole-body metabolic fate of branched-chain amino acids[J]. Biochem J，2021，478（4）：765-776.
[9] MCCANN J R，BIHLMEYER N A，ROCHE K，et al. The pediatric obesity microbiome and metabolism study（POMMS）：methods，baseline data，and early insights[J]. Obesity（Silver Spring），2021，29（3）：569-578.
[10] SUN H P，OLSON K C，GAO C，et al. Catabolic defect of branched-chain amino acids promotes heart failure[J]. Circulation，2016，133（21）：2038-2049.
[11] ANG Q Y，ALEXANDER M，NEWMAN J C，et al. Ketogenic diets alter the gut microbiome resulting in decreased intestinal Th17 cells[J/OL]. Cell，2020，181（6）：1263-1275，e16[2023-11-01]. https://doi.org/10.1016/j.cell.2020.04.027.
[12] BELL J A，BULL C J，GUNTER M J，et al. Early metabolic features of genetic liability to type 2 diabetes：cohort study with repeated metabolomics across early life[J]. Diabetes Care，2020，43（7）：1537-1545.
[13] FELIG P，MARLISS E，CAHILL G F，Jr. Plasma amino acid levels and insulin secretion in obesity[J]. N Engl J Med，1969，281（15）：811-816.
[14] NEWGARD C B，AN J，BAIN J R，et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance[J]. Cell Metab，2009，9（4）：311-326.
[15] WANG T J，LARSON M G，VASAN R S，et al. Metabolite profiles and the risk of developing diabetes[J]. Nat Med，2011，17（4）：448-453.
[16] SHAH S H，BAIN J R，MUEHLBAUER M J，et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events[J]. Circ Cardiovasc Genet，2010，3（2）：207-214.
[17] LISCHKA J，SCHANZER A，HOJREH A，et al. A branched-chain amino acid-based metabolic score can predict liver fat in children and adolescents with severe obesity[J/OL]. Pediatr Obes，2021，16（4）：e12739[2023-11-01]. https://doi.org/10.1111/ijpo.12739.
[18] PENG K Y，WATT M J，RENSEN S，et al. Mitochondrial dysfunction-related lipid changes occur in nonalcoholic fatty liver disease progression[J]. J Lipid Res，2018，59（10）：1977-1986.
[19] SHAH S H，SUN J L，STEVENS R D，et al. Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease[J/OL]. Am Heart J，2012，163（5）：844-850，e1[2023-11-01]. https://doi.org/10.1016/j.ahj.2012.02.005.
[20] MCGARRAH R W，ZHANG G F，CHRISTOPHER B A，et al. Dietary branched-chain amino acid restriction alters fuel selection and reduces triglyceride stores in hearts of Zucker fatty rats[J/OL]. Am J Physiol Endocrinol Metab，2020，318（2）：E216-E223[2023-11-01]. https://doi.org/10.1152/ajpendo.00334.2019.
[21] WHITE P J，LAPWORTH A L，MCGARRAH R W，et al. Muscle-liver trafficking of BCAA-derived nitrogen underlies obesity-related glycine depletion
[J/OL]. Cell Rep，2020，33（6）：108375[2023-11-01]. https://doi.org/10.1016/j.celrep.2020.108375.
[22] WHITE P J，MCGARRAH R W，GRIMSRUD P A，et al. The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase[J/OL]. Cell Metab，2018，27（6）：1281-1293，e1-e7[2023-11-01]. https://doi.org/10.1016/j.cmet. 2018.04.015.
[23] WHITE P J，MCGARRAH R W，HERMAN M A，et al. Insulin action，type 2 diabetes，and branched-chain amino acids：a two-way street[J/OL]. Mol Metab，2021，52：101261[2023-11-01]. https://doi.org/10.1016/j.molmet.2021.101261.
[24] LI X，SUN D J Y，ZHOU T，et al. Changes of branched-chain amino acids and ectopic fat in response to weight-loss diets：the POUNDS lost trial[J/OL]. J Clin Endocrinol Metab，2020，105（10）：e3747-e3756[2023-11-01].
https://doi.org/10.1210/clinem/dgaa377.
[25] KARUSHEVA Y，KOESSLER T，STRASSBURGER K，et al. Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes：a randomized controlled crossover trial[J]. Am J Clin Nutr，2019，110（5）：1098-1107.
[26] SAMCZUK P，HADY H R，ADAMSKA-PATRUNO E，et al. In-and-out molecular changes linked to the type 2 diabetes remission after bariatric surgery：an influence of gut microbes on mitochondria metabolism[J]. Int J Mol Sci，2018，19（12）：3744.
[27] SUMMERS S A，CHAURASIA B，HOLLAND W L. Metabolic messengers：ceramides[J]. Nat Metab，2019，1（11）：1051-1058.
[28] CHOI R H，TATUM S M，SYMONS J D，et al. Ceramides and other sphingolipids as drivers of cardiovascular disease[J]. Nat Rev Cardiol，2021，18（10）：701-711.
[29] GREEN C D，MACEYKA M，COWART L A，et al. Sphingolipids in metabolic disease：the good，the bad，and the unknown[J]. Cell Metab，2021，33（7）：1293-1306.
[30] LI J，XIE L M，SONG J L，et al. Alterations of sphingolipid metabolism in different types of polycystic ovary syndrome[J]. Sci Rep，2019，9（1）：3204.
[31] MEIKLE P J，SUMMERS S A. Sphingolipids and phospholipids in insulin resistance and related metabolic disorders[J]. Nat Rev Endocrinol，2017，13（2）：79-91.
[32] HILVO M，VASILE V C，DONATO L J，et al. Ceramides and ceramide scores：clinical applications for cardiometabolic risk stratification[J/OL]. Front Endocrinol（Lausanne），2020，11：570628[2023-11-01]. https://doi.org/10.3389/fendo.2020.570628.
[33] LAAKSONEN R，EKROOS K，SYSI-AHO M，et al. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol[J]. Eur Heart J，2016，37（25）：1967-1976.
[34] TIPPETTS T S，HOLLAND W L，SUMMERS S A. The ceramide ratio：a predictor of cardiometabolic risk[J]. J Lipid Res，2018，59（9）：1549-1550.
[35] TURPIN S M，NICHOLLS H T，WILLMES D M，et al. Obesity-induced CerS6-dependent C16：0 ceramide production promotes weight gain and glucose intolerance[J]. Cell Metab，2014，20（4）：678-686.
[36] RAICHUR S，WANG S T，CHAN P W，et al. CerS2 haploinsufficiency inhibits β-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance[J]. Cell Metab，2014，20（4）：687-695.
[37] KLEIBOEKER B，LODHI I J. Peroxisomal regulation of energy homeostasis：effect on obesity and related metabolic disorders[J/OL]. Mol Metab，2022，65：101577
[2023-11-01]. https://doi.org/10.1016/j.molmet.2022.101577.
[38] COOK H W，THOMAS S E，XU Z. Essential fatty acids and serine as plasmalogen precursors in relation to competing metabolic pathways[J]. Biochem Cell Biol，1991，69（7）：475-484.
[39] WITTENBECHER C，GUASCH-FERRÉ M，HASLAM D E，et al. Changes in metabolomics profiles over ten years and subsequent risk of developing type 2 diabetes：results from the nurses’ health study
[J/OL]. EBioMedicine，2022，75：103799[2023-11-01].
https://doi.org/10.1016/j.ebiom.2021.103799.
[40] HAYASHI M，KUDO M，GAO M. Plasmalogen inhibits body weight gain by activating brown adipose tissue and improving white adipose tissue metabolism[J]. J Nutr Sci Vitaminol（Tokyo），2022，68（2）：140-147.
[41] LANKINEN M，SCHWAB U，KOLEHMAINEN M，et al. A healthy Nordic diet alters the plasma lipidomic profile in adults with features of metabolic syndrome in a multicenter randomized dietary intervention[J]. J Nutr，2015，146（4）：662-672.
[42] OLSON E，SUH J H，SCHWARZ J M，et al. Effects of isocaloric fructose restriction on ceramide levels in children with obesity and cardiometabolic risk：relation to hepatic de novo lipogenesis and insulin sensitivity[J]. Nutrients，2022，14（7）：1432.
[43] MARKLUND M，WU J H Y，IMAMURA F，et al. Biomarkers of dietary omega-6 fatty acids and incident cardiovascular disease and mortality[J]. Circulation，2019，139（21）：2422-2436.
[44] SUN D，TIEDT S，YU B，et al. A prospective study of serum metabolites and risk of ischemic stroke[J/OL]. Neurology，2019，92（16）：e1890-e1898[2023-11-01]. https://doi.org/10.1212/WNL.0000000000007279.
[45] CHOI J Y，KIM J S，KIM J H，et al. High free fatty acid level is associated with recurrent stroke in cardioembolic stroke patients[J]. Neurology，2014，82（13）：1142-1148.