Natasha Z. Anita , Nathan Herrmann , Si Won Ryoo , Chelsi Major-Orfao , William Z. Lin , Felicia Kwan , Shiropa Noor , Jennifer S. Rabin , Susan Marzolini , Sean Nestor , Myuri T. Ruthirakuhan , Bradley J. MacIntosh , Maged Goubran , Pearl Yang , Hugo Cogo-Moreira , Mark Rapoport , Damien Gallagher , Sandra E. Black , Benjamin I. Goldstein , Krista L. Lanctôt , Walter Swardfager
{"title":"细胞色素 P450-可溶性环氧化物水解酶氧化脂、2 型糖尿病患者的抑郁和认知。","authors":"Natasha Z. Anita , Nathan Herrmann , Si Won Ryoo , Chelsi Major-Orfao , William Z. Lin , Felicia Kwan , Shiropa Noor , Jennifer S. Rabin , Susan Marzolini , Sean Nestor , Myuri T. Ruthirakuhan , Bradley J. MacIntosh , Maged Goubran , Pearl Yang , Hugo Cogo-Moreira , Mark Rapoport , Damien Gallagher , Sandra E. Black , Benjamin I. Goldstein , Krista L. Lanctôt , Walter Swardfager","doi":"10.1016/j.jdiacomp.2024.108826","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><p>This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM).</p></div><div><h3>Methods</h3><p>Clinically cognitively normal T2DM individuals were recruited (<span><span>NCT04455867</span><svg><path></path></svg></span>). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry.</p></div><div><h3>Results</h3><p>The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F<sub>1,101</sub> = 6.094, <em>p</em> = 0.015 and F<sub>1,101</sub> = 5.598, <em>p</em> = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F<sub>1,100</sub> = 12.137, <em>p</em> < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F<sub>1,100</sub> = 6.481, <em>p</em> = 0.012) and 11(12)-EpETrE (F<sub>1,100</sub> = 4.409, <em>p</em> = 0.038), and 2) verbal memory, including 9(10)-EpOME (F<sub>1,100</sub> = 4.286, <em>p</em> = 0.041), 5(6)-EpETrE (F<sub>1,100</sub> = 6.845, <em>p</em> = 0.010), 11(12)-EpETrE (F<sub>1,100</sub> = 3.981, <em>p</em> = 0.049) and 14(15)-EpETrE (F<sub>1,100</sub> = 5.019, <em>p</em> = 0.027).</p></div><div><h3>Conclusions</h3><p>Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.</p></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"38 9","pages":"Article 108826"},"PeriodicalIF":2.9000,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1056872724001521/pdfft?md5=b48c09117a48aa4b6ee187f5254cb133&pid=1-s2.0-S1056872724001521-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes\",\"authors\":\"Natasha Z. Anita , Nathan Herrmann , Si Won Ryoo , Chelsi Major-Orfao , William Z. Lin , Felicia Kwan , Shiropa Noor , Jennifer S. Rabin , Susan Marzolini , Sean Nestor , Myuri T. Ruthirakuhan , Bradley J. MacIntosh , Maged Goubran , Pearl Yang , Hugo Cogo-Moreira , Mark Rapoport , Damien Gallagher , Sandra E. Black , Benjamin I. Goldstein , Krista L. Lanctôt , Walter Swardfager\",\"doi\":\"10.1016/j.jdiacomp.2024.108826\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><p>This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM).</p></div><div><h3>Methods</h3><p>Clinically cognitively normal T2DM individuals were recruited (<span><span>NCT04455867</span><svg><path></path></svg></span>). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry.</p></div><div><h3>Results</h3><p>The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F<sub>1,101</sub> = 6.094, <em>p</em> = 0.015 and F<sub>1,101</sub> = 5.598, <em>p</em> = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F<sub>1,100</sub> = 12.137, <em>p</em> < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F<sub>1,100</sub> = 6.481, <em>p</em> = 0.012) and 11(12)-EpETrE (F<sub>1,100</sub> = 4.409, <em>p</em> = 0.038), and 2) verbal memory, including 9(10)-EpOME (F<sub>1,100</sub> = 4.286, <em>p</em> = 0.041), 5(6)-EpETrE (F<sub>1,100</sub> = 6.845, <em>p</em> = 0.010), 11(12)-EpETrE (F<sub>1,100</sub> = 3.981, <em>p</em> = 0.049) and 14(15)-EpETrE (F<sub>1,100</sub> = 5.019, <em>p</em> = 0.027).</p></div><div><h3>Conclusions</h3><p>Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.</p></div>\",\"PeriodicalId\":15659,\"journal\":{\"name\":\"Journal of diabetes and its complications\",\"volume\":\"38 9\",\"pages\":\"Article 108826\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1056872724001521/pdfft?md5=b48c09117a48aa4b6ee187f5254cb133&pid=1-s2.0-S1056872724001521-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of diabetes and its complications\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1056872724001521\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of diabetes and its complications","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1056872724001521","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes
Aims
This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM).
Methods
Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry.
Results
The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F1,101 = 6.094, p = 0.015 and F1,101 = 5.598, p = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F1,100 = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F1,100 = 6.481, p = 0.012) and 11(12)-EpETrE (F1,100 = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F1,100 = 4.286, p = 0.041), 5(6)-EpETrE (F1,100 = 6.845, p = 0.010), 11(12)-EpETrE (F1,100 = 3.981, p = 0.049) and 14(15)-EpETrE (F1,100 = 5.019, p = 0.027).
Conclusions
Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.
期刊介绍：
Journal of Diabetes and Its Complications (JDC) is a journal for health care practitioners and researchers, that publishes original research about the pathogenesis, diagnosis and management of diabetes mellitus and its complications. JDC also publishes articles on physiological and molecular aspects of glucose homeostasis.
The primary purpose of JDC is to act as a source of information usable by diabetes practitioners and researchers to increase their knowledge about mechanisms of diabetes and complications development, and promote better management of people with diabetes who are at risk for those complications.
Manuscripts submitted to JDC can report any aspect of basic, translational or clinical research as well as epidemiology. Topics can range broadly from early prediabetes to late-stage complicated diabetes. Topics relevant to basic/translational reports include pancreatic islet dysfunction and insulin resistance, altered adipose tissue function in diabetes, altered neuronal control of glucose homeostasis and mechanisms of drug action. Topics relevant to diabetic complications include diabetic retinopathy, neuropathy and nephropathy; peripheral vascular disease and coronary heart disease; gastrointestinal disorders, renal failure and impotence; and hypertension and hyperlipidemia.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
