Presentation Date
13-10-2022 12:00 AM
Description
Abnormal lipid metabolism is the derivation of multiple retinal degenerative and blinding diseases. The membrane-type frizzled-related protein (MFRP), and adiponectin receptor 1 (AdipoR1) were shown to be vital to the maintenance of a healthy retinal lipidome. The two mice models of retinal degenerations Mfrprd6 and Adipor1 -/- resulted in a reduction of phospholipids containing docosahexaenoic acid (DHA; 22:6) and very long-chain polyunsaturated fatty acids (VLC-PUFAs). In a pathway involving the ω-3 fatty acids eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6), the fatty acid elongase-4 (ELOVL4) elongates the fatty acid 28:6 into VLC-PUFAs, which are precursors to potent neuroprotective molecules known as Elovanoids. Given that these lipids are essential for proper vision, it is important to compare the amount of the total fatty acids in the ω-3 and ω-6 pathways in Mfrprd6 and Adipor1 -/- . We isolated retina and RPE-eyecups from 6-week-old Mfrprd6, Adipor1 -/-, and control mice and extracted the lipids followed by alkaline hydrolysis and analyzed it via for LC-MS/MS. Total fatty acids showed a significant decrease in the fatty acids in fatty acids 24:6n3 to 36:6n3 in the retina for both the Mfrprd6 and Adipor1 -/- . For the RPE samples, there was a specific decrease in 32:6n3 and 34:6n3. Interestingly, Mfrprd6 showed elevated levels of 22:5n3 and 24:5n3 in the retina. In contrast, Adipor1 -/- showed decreased levels of 22:5n3 and 24:5n3 in the retina. Additionally, arachidonic acid (20:4n6), 22:4n6, and 24:4n6 were elevated in Mfrprd6 retina. Our study demonstrated that both Mfrprd6 and Adipor1 -/- had depleted levels of VLC-PUFAs from 24:6n3 onwards, suggesting a decreased ability to synthesize Elovanoids which require the precursors 32:6n3 and 34:6n3. Given that there was a buildup of 24:5n3 in Mfrprd retina, the conversion of 24:5n3 to 24:6n3 seems to be impaired in animals with Mfrprd6. In contrast, the levels of PUFAs in Adipor1 -/- retina were low from 20:5n3 to 36:6n3. In Mfrprd retina, there were increased levels of arachidonic acid and its downstream products. Despite the implications of both models in retinal degeneration, there were significant differences along the ω-3 and ω-6 biosynthesis pathways. The next step in our project will attempt to clarify these lipid synthesis pathways using deuterium starting products.
Recommended Citation
Aucoin, Alise J.; Kautzmann Guerin, Marie-Audrey; Gordon, William; Prestenburg, Eric; Ji, Jeff; Perera, Rasangi; and Bazan, Nicolas, "Retinal degeneration in mice devoid of membrane-type frizzled-related proteinor adiponectin receptor 1 results in selective fatty acid synthesis impairments" (2022). Medical Research Day. 4.
https://digitalscholar.lsuhsc.edu/sommrd/2022MRD/Posters/4
Included in
Retinal degeneration in mice devoid of membrane-type frizzled-related proteinor adiponectin receptor 1 results in selective fatty acid synthesis impairments
Abnormal lipid metabolism is the derivation of multiple retinal degenerative and blinding diseases. The membrane-type frizzled-related protein (MFRP), and adiponectin receptor 1 (AdipoR1) were shown to be vital to the maintenance of a healthy retinal lipidome. The two mice models of retinal degenerations Mfrprd6 and Adipor1 -/- resulted in a reduction of phospholipids containing docosahexaenoic acid (DHA; 22:6) and very long-chain polyunsaturated fatty acids (VLC-PUFAs). In a pathway involving the ω-3 fatty acids eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6), the fatty acid elongase-4 (ELOVL4) elongates the fatty acid 28:6 into VLC-PUFAs, which are precursors to potent neuroprotective molecules known as Elovanoids. Given that these lipids are essential for proper vision, it is important to compare the amount of the total fatty acids in the ω-3 and ω-6 pathways in Mfrprd6 and Adipor1 -/- . We isolated retina and RPE-eyecups from 6-week-old Mfrprd6, Adipor1 -/-, and control mice and extracted the lipids followed by alkaline hydrolysis and analyzed it via for LC-MS/MS. Total fatty acids showed a significant decrease in the fatty acids in fatty acids 24:6n3 to 36:6n3 in the retina for both the Mfrprd6 and Adipor1 -/- . For the RPE samples, there was a specific decrease in 32:6n3 and 34:6n3. Interestingly, Mfrprd6 showed elevated levels of 22:5n3 and 24:5n3 in the retina. In contrast, Adipor1 -/- showed decreased levels of 22:5n3 and 24:5n3 in the retina. Additionally, arachidonic acid (20:4n6), 22:4n6, and 24:4n6 were elevated in Mfrprd6 retina. Our study demonstrated that both Mfrprd6 and Adipor1 -/- had depleted levels of VLC-PUFAs from 24:6n3 onwards, suggesting a decreased ability to synthesize Elovanoids which require the precursors 32:6n3 and 34:6n3. Given that there was a buildup of 24:5n3 in Mfrprd retina, the conversion of 24:5n3 to 24:6n3 seems to be impaired in animals with Mfrprd6. In contrast, the levels of PUFAs in Adipor1 -/- retina were low from 20:5n3 to 36:6n3. In Mfrprd retina, there were increased levels of arachidonic acid and its downstream products. Despite the implications of both models in retinal degeneration, there were significant differences along the ω-3 and ω-6 biosynthesis pathways. The next step in our project will attempt to clarify these lipid synthesis pathways using deuterium starting products.
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