Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes
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 T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cogniti...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000688 |
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| author | Natasha Z. Anita Felicia Kwan Si Won Ryoo Chelsi Major-Orfao William Z. Lin Shiropa Noor Krista L. Lanctôt Nathan Herrmann Paul I. Oh Baiju R. Shah Jeremy Gilbert Angela Assal Ilana J. Halperin Ameer Y. Taha Walter Swardfager |
| author_facet | Natasha Z. Anita Felicia Kwan Si Won Ryoo Chelsi Major-Orfao William Z. Lin Shiropa Noor Krista L. Lanctôt Nathan Herrmann Paul I. Oh Baiju R. Shah Jeremy Gilbert Angela Assal Ilana J. Halperin Ameer Y. Taha Walter Swardfager |
| author_sort | Natasha Z. Anita |
| collection | DOAJ |
| description | 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 T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second 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. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F1,98 = 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 (F1,98 = 7.222, P = 0.008 and F1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent. |
| first_indexed | 2024-03-12T22:46:46Z |
| format | Article |
| id | doaj.art-059402781c494403995441497ba00b47 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-12T22:46:46Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-059402781c494403995441497ba00b472023-07-21T04:57:38ZengElsevierJournal of Lipid Research0022-22752023-07-01647100395Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetesNatasha Z. Anita0Felicia Kwan1Si Won Ryoo2Chelsi Major-Orfao3William Z. Lin4Shiropa Noor5Krista L. Lanctôt6Nathan Herrmann7Paul I. Oh8Baiju R. Shah9Jeremy Gilbert10Angela Assal11Ilana J. Halperin12Ameer Y. Taha13Walter Swardfager14Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, CanadaKITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, CanadaSunnybrook Research Institute, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Health Sciences Centre, Toronto, ON, CanadaDepartment of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA; West Coast Metabolomics Center, Genome Center, University of California, Davis, Davis, CA, USA; Center for Neuroscience, University of California, Davis, Davis, CA, USADepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, Canada; For correspondence: Walter SwardfagerType 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 T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second 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. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F1,98 = 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 (F1,98 = 7.222, P = 0.008 and F1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent.http://www.sciencedirect.com/science/article/pii/S0022227523000688Alzheimer’s diseaseinflammationlipidsobesityoxidized lipids |
| spellingShingle | Natasha Z. Anita Felicia Kwan Si Won Ryoo Chelsi Major-Orfao William Z. Lin Shiropa Noor Krista L. Lanctôt Nathan Herrmann Paul I. Oh Baiju R. Shah Jeremy Gilbert Angela Assal Ilana J. Halperin Ameer Y. Taha Walter Swardfager Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes Journal of Lipid Research Alzheimer’s disease inflammation lipids obesity oxidized lipids |
| title | Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes |
| title_full | Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes |
| title_fullStr | Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes |
| title_full_unstemmed | Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes |
| title_short | Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes |
| title_sort | cytochrome p450 soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes |
| topic | Alzheimer’s disease inflammation lipids obesity oxidized lipids |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000688 |
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