Metabolism of omega-3 fatty acids in carriers of apolipoprotein E epsilon 4

According to world health organization, 50 million individuals live with dementia, where Alzheimer’s disease represents 60 to 70% of those cases. Carrying the apolipoprotein E epsilon 4 allele (APOE4) is the main genetic risk factor for late onset Alzheimer’s disease. Studies have found that consuming a diet rich in omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can decrease the risk of developing Alzheimer’s disease. However, the benefit of consuming omega-3 fatty acids is not seen in APOE4 carriers. Additionally, studies have demonstrated that brain can take-in fatty acids in the lysophosphatidylcholine (LPC) and free fatty acid (FFA) compartments. Therefore, we hypothesized that after consuming omega-3 fatty acid supplements for six months, APOE4 carriers’ plasma omega-3 fatty acid levels would not increase in the LPC and FFA plasma lipid compartments compared to non-carriers of the APOE4. To investigate this, we analysed DHA and EPA concentrations in the following plasma lipid compartments: LPC, phosphatidylcholine (PC), phosphatidylethanolamine (PE), FFA, triglyceride (TG) and cholesteryl esters (CE). Firstly, lipids were extracted from the plasma and then separated into CE, TG, FFA, and PL using thin layer chromatography. PL were further separated into PE, PC and LPC using a second thin layer chromatography plate. The fatty acids in the separated lipid compartments were converted to fatty acid methyl ester to be analysed using gas chromatography. In the current study, post-omega-3 fatty acid supplementation for six months, plasma DHA and EPA levels increased in all the lipid compartments analyzed. Additionally, there was a genotype trend for DHA in CE, where APOE4 carriers had higher levels of DHA compared to non-carriers before and after omega-3 supplementation. When comparing ΔDHA and ΔEPA (pre – post concentration) in the different lipid compartments between low and high body mass index (BMI) groups (<25.2 kg/m2 and >25.2 kg/m2, respectively) and genotype, plasma concentration of DHA and EPA in LPC of individuals in the high BMI group did not increase as much as those in the low BMI group after taking omega-3 fatty acids. Therefore, individuals in the high BMI group had less DHA available in the lipid compartment the brain can take-in. In conclusion, our research hypothesis is rejected as our results suggests supplementation with omega-3 fatty acids could benefit APOE4 carriers since DHA and EPA levels are higher in the plasma compartments where uptake of omega-3 fatty acids are possible by the brain.

Name thesis:degree_name

M. Sc.

Level thesis:degree_level

Maîtrise

Discipline thesis:degree_discipline

Physiologie

Grantor dc:publisher

Université de Sherbrooke

Year dc:date.issued

2021

Author dc:creator

• Balakrishnan, Janani

Advisor dc:contributor.advisor

• Plourde, Mélanie

• Omega-3 fatty acids
• Fatty acid metabolism
• APOE4
• Cognitive decline
• Alzheimer's disease
• Acides gras oméga-3
• Métabolisme des acides gras
• Déclin cognitive

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/2.5/ca/

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/11143/18383

OAI identifier oai:identifier

oai:usherbrooke.scholaris.ca:11143/18383