Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes

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

Journal of Lipid Research (Jul 2023)

Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes

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

Affiliations

Natasha Z. Anita: Department 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
Felicia Kwan: Department 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
Si Won Ryoo: Department 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
Chelsi Major-Orfao: Sunnybrook Research Institute, Toronto, ON, Canada; KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, Canada
William Z. Lin: Department 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
Shiropa Noor: Department 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
Krista L. Lanctôt: Department 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, Canada
Nathan Herrmann: Sunnybrook Research Institute, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Paul I. Oh: KITE Research Institute, Toronto Rehabilitation Institute-University Health Network, Toronto, ON, Canada
Baiju R. Shah: Sunnybrook Research Institute, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Jeremy Gilbert: Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Angela Assal: Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Ilana J. Halperin: Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Ameer Y. Taha: Department 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, USA
Walter Swardfager: Department 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 Swardfager

Journal volume & issue: Vol. 64, no. 7
p. 100395

Abstract

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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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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