Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications Pub Date : 2024-07-22 DOI:10.1016/j.jdiacomp.2024.108826

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

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Abstract

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 (F_1,101 = 6.094, p = 0.015 and F_1,101 = 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 (F_1,100 = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F_1,100 = 6.481, p = 0.012) and 11(12)-EpETrE (F_1,100 = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F_1,100 = 4.286, p = 0.041), 5(6)-EpETrE (F_1,100 = 6.845, p = 0.010), 11(12)-EpETrE (F_1,100 = 3.981, p = 0.049) and 14(15)-EpETrE (F_1,100 = 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.

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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。

目的：本研究探讨了血清细胞色素P450-可溶性环氧化物水解酶（CYP450-sEH）氧化脂蛋白和抑郁症状与2型糖尿病（T2DM）患者认知能力的关系：招募临床认知能力正常的 T2DM 患者（NCT04455867）。使用贝克抑郁量表-II（BDI-II；总分≤13分表示抑郁症状轻微，≥14分表示抑郁症状严重）评估抑郁症状严重程度。对执行功能和言语记忆进行了评估。采用超高效液相色谱串联质谱法对空腹血清中的氧脂进行定量：研究包括 85 名抑郁症状轻微的参与者和 27 名抑郁症状明显的参与者（平均年龄：63.3 ± 9.8 岁，49% 为女性）。在所有参与者中，亚油酸衍生的sEH（12,13-二羟基十八碳烯酸；DiHOME）和CYP450（12(13)-环氧十八碳烯酸；EPOME）代谢物浓度较高与执行功能较差有关（分别为F1,101 = 6.094，p = 0.015和F1,101 = 5.598，p = 0.020）。多种 sEH 底物的浓度与抑郁症状相互作用，可预测 1) 较差的执行功能，包括 9(10)-EpOME (F1,100 = 12.137, p 1,100 = 6.481, p = 0.012) 和 11(12)-EpETrE (F1,100 = 4.409, p = 0. 038)，以及 2) 言语功能。038），以及 2) 言语记忆，包括 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) 和 14(15)-EpETrE (F1,100 = 5.019, p = 0.027)：CYP450-sEH代谢物和抑郁症状与认知的关联凸显了CYP450-sEH途径在T2DM中的生物标记和治疗潜力。

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来源期刊

Journal of diabetes and its complications 医学-内分泌学与代谢

CiteScore

5.90

自引率

3.30%

发文量

153

审稿时长

16 days

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.