Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes.
J Diabetes Complications
; 38(9): 108826, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-39059187
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 (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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cytochrome P-450 enzyme system
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Dépression
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Diabète de type 2
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Epoxide hydrolase
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Oxylipines
Limites:
Aged
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Female
/
Humans
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Male
/
Middle aged
Langue:
En
Journal:
J Diabetes Complications
Sujet du journal:
ENDOCRINOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Canada
Pays de publication:
États-Unis d'Amérique