Anita_2023_J.Lipid.Res__100395

Reference

Title : Cytochrome p450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes - Anita_2023_J.Lipid.Res__100395
Author(s) : Anita NZ , Kwan F , Ryoo SW , Major-Orfao C , Lin WZ , Noor S , Lanctot KL , Herrmann N , Oh PI , Shah BR , Gilbert J , Assal A , Halperin IJ , Taha AY , Swardfager W
Ref : J Lipid Res , :100395 , 2023
Abstract :

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in both T2DM and cognitive impairment. Obesity is common in this population and it has been associated with altered oxylipin concentrations. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in people with T2DM, and explore potential differences between obese and non-obese individuals. The study included 51 obese and 57 non-obese participants (mean age 63.0+/-9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test (Victoria Version), FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, 2(nd) Edition. Four LA-derived oxylipins were analyzed by ultra-high pressure-LC/MS, and the 12,13-dihydroxyoctadecamonoenoic acid (12,13-DiHOME) considered the main species of interest. All models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and years of education. The sEH-derived 12,13-DiHOME was associated with lower executive function scores (F(1,98)=7.513, p=0.007). The CYP450-derived 12(13)-epoxyoctadecamonoenoic acid (12(13)-EpOME) was associated with poorer executive function and verbal memory scores (F(1,98)=7.222, p=0.008 and F(1,98)=4.621, p=0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F(1,97)=5.498, p=0.021), and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F(1,97)=4.126, p=0.045) predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway may be a potential therapeutic target for cognitive decline in T2DM, and for some markers relationships may be obesity-dependent.

PubMedSearch : Anita_2023_J.Lipid.Res__100395
PubMedID: 37245563

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Anita NZ, Kwan F, Ryoo SW, Major-Orfao C, Lin WZ, Noor S, Lanctot KL, Herrmann N, Oh PI, Shah BR, Gilbert J, Assal A, Halperin IJ, Taha AY, Swardfager W (2023)
Cytochrome p450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes
J Lipid Res :100395

Anita NZ, Kwan F, Ryoo SW, Major-Orfao C, Lin WZ, Noor S, Lanctot KL, Herrmann N, Oh PI, Shah BR, Gilbert J, Assal A, Halperin IJ, Taha AY, Swardfager W (2023)
J Lipid Res :100395