The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice
The apolipoprotein E4 (<i>APOE4</i>) genotype is predictive of Alzheimer’s disease (AD). The brain is highly enriched with the omega-3 polyunsaturated fatty acid (n3-PUFA), docosahexaenoic acid (DHA). DHA’s metabolism is defective in <i>APOE4</i> carriers. Flavanol intake can...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/15/9/2032 |
| _version_ | 1797601994782801920 |
|---|---|
| author | Anneloes Martinsen Rasha N. M. Saleh Raphael Chouinard-Watkins Richard Bazinet Glenn Harden James Dick Noemi Tejera Matthew G. Pontifex David Vauzour Anne-Marie Minihane |
| author_facet | Anneloes Martinsen Rasha N. M. Saleh Raphael Chouinard-Watkins Richard Bazinet Glenn Harden James Dick Noemi Tejera Matthew G. Pontifex David Vauzour Anne-Marie Minihane |
| author_sort | Anneloes Martinsen |
| collection | DOAJ |
| description | The apolipoprotein E4 (<i>APOE4</i>) genotype is predictive of Alzheimer’s disease (AD). The brain is highly enriched with the omega-3 polyunsaturated fatty acid (n3-PUFA), docosahexaenoic acid (DHA). DHA’s metabolism is defective in <i>APOE4</i> carriers. Flavanol intake can play a role in modulating DHA levels. However, the impact of flavanol co-supplementation with fish oil on brain DHA uptake, status and partitioning, and according to <i>APOE</i> genotype is currently unknown. Here, using a humanised <i>APOE3</i> and <i>APOE4</i> targeted replacement transgenic mouse model, the interactive influence of cocoa flavanols (FLAV) and <i>APOE</i> genotype on the blood and subcortical brain PUFA status following the supplementation of a high fat (HF) enriched with DHA from fish oil (FO) was investigated. DHA levels increased in the blood (<i>p</i> < 0.001) and brain (<i>p</i> = 0.001) following supplementation. Compared to <i>APOE3,</i> a higher red blood cell (RBC) DHA (<i>p</i> < 0.001) was evident in <i>APOE4</i> mice following FO and FLAV supplementation. Although FO did not increase the percentage of brain DHA in <i>APOE4,</i> a 17.1% (<i>p</i> < 0.05) and 20.0% (<i>p</i> < 0.001) higher DHA level in the phosphatidylcholine (PC) fraction in the HF FO and HF FO FLAV groups, and a 14.5% (<i>p</i> < 0.05) higher DHA level in the phosphatidylethanolamine (PE) fraction in the HF FO FLAV group was evident in these animals relative to the HF controls. The addition of FLAV (+/− FO) did not significantly increase the percentage of brain DHA in the group as a whole. However, a higher brain: RBC DHA ratio was evident in <i>APOE3</i> only (<i>p</i> < 0.05) for HF FLAV versus HF. In conclusion, our data shows only modest effects of FLAV on the brain DHA status, which is limited to <i>APOE3.</i> |
| first_indexed | 2024-03-11T04:10:59Z |
| format | Article |
| id | doaj.art-520b29d717d441fd8f1331a5a9a75aa7 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T04:10:59Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-520b29d717d441fd8f1331a5a9a75aa72023-11-17T23:28:12ZengMDPI AGNutrients2072-66432023-04-01159203210.3390/nu15092032The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic MiceAnneloes Martinsen0Rasha N. M. Saleh1Raphael Chouinard-Watkins2Richard Bazinet3Glenn Harden4James Dick5Noemi Tejera6Matthew G. Pontifex7David Vauzour8Anne-Marie Minihane9Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNutrition Analytical Service, Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKThe apolipoprotein E4 (<i>APOE4</i>) genotype is predictive of Alzheimer’s disease (AD). The brain is highly enriched with the omega-3 polyunsaturated fatty acid (n3-PUFA), docosahexaenoic acid (DHA). DHA’s metabolism is defective in <i>APOE4</i> carriers. Flavanol intake can play a role in modulating DHA levels. However, the impact of flavanol co-supplementation with fish oil on brain DHA uptake, status and partitioning, and according to <i>APOE</i> genotype is currently unknown. Here, using a humanised <i>APOE3</i> and <i>APOE4</i> targeted replacement transgenic mouse model, the interactive influence of cocoa flavanols (FLAV) and <i>APOE</i> genotype on the blood and subcortical brain PUFA status following the supplementation of a high fat (HF) enriched with DHA from fish oil (FO) was investigated. DHA levels increased in the blood (<i>p</i> < 0.001) and brain (<i>p</i> = 0.001) following supplementation. Compared to <i>APOE3,</i> a higher red blood cell (RBC) DHA (<i>p</i> < 0.001) was evident in <i>APOE4</i> mice following FO and FLAV supplementation. Although FO did not increase the percentage of brain DHA in <i>APOE4,</i> a 17.1% (<i>p</i> < 0.05) and 20.0% (<i>p</i> < 0.001) higher DHA level in the phosphatidylcholine (PC) fraction in the HF FO and HF FO FLAV groups, and a 14.5% (<i>p</i> < 0.05) higher DHA level in the phosphatidylethanolamine (PE) fraction in the HF FO FLAV group was evident in these animals relative to the HF controls. The addition of FLAV (+/− FO) did not significantly increase the percentage of brain DHA in the group as a whole. However, a higher brain: RBC DHA ratio was evident in <i>APOE3</i> only (<i>p</i> < 0.05) for HF FLAV versus HF. In conclusion, our data shows only modest effects of FLAV on the brain DHA status, which is limited to <i>APOE3.</i>https://www.mdpi.com/2072-6643/15/9/2032Alzheimer’s diseaseapolipoprotein Edocosahexaenoic acidbrainflavonoidsphospholipids |
| spellingShingle | Anneloes Martinsen Rasha N. M. Saleh Raphael Chouinard-Watkins Richard Bazinet Glenn Harden James Dick Noemi Tejera Matthew G. Pontifex David Vauzour Anne-Marie Minihane The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice Nutrients Alzheimer’s disease apolipoprotein E docosahexaenoic acid brain flavonoids phospholipids |
| title | The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice |
| title_full | The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice |
| title_fullStr | The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice |
| title_full_unstemmed | The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice |
| title_short | The Influence of <i>APOE</i> Genotype, DHA, and Flavanol Intervention on Brain DHA and Lipidomics Profile in Aged Transgenic Mice |
| title_sort | influence of i apoe i genotype dha and flavanol intervention on brain dha and lipidomics profile in aged transgenic mice |
| topic | Alzheimer’s disease apolipoprotein E docosahexaenoic acid brain flavonoids phospholipids |
| url | https://www.mdpi.com/2072-6643/15/9/2032 |
| work_keys_str_mv | AT anneloesmartinsen theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT rashanmsaleh theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT raphaelchouinardwatkins theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT richardbazinet theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT glennharden theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT jamesdick theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT noemitejera theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT matthewgpontifex theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT davidvauzour theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT annemarieminihane theinfluenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT anneloesmartinsen influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT rashanmsaleh influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT raphaelchouinardwatkins influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT richardbazinet influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT glennharden influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT jamesdick influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT noemitejera influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT matthewgpontifex influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT davidvauzour influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice AT annemarieminihane influenceofiapoeigenotypedhaandflavanolinterventiononbraindhaandlipidomicsprofileinagedtransgenicmice |