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Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice.

ABSTRACT: Objective:To evaluate the therapeutic effects of omega-3 (?3) fatty acids in the retina of aged mice when the blood arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is maintained between 1.0 and 1.5. Methods and analysis:Aged (24-month-old) wild-type C57BL/6J mice were allocated to two groups: ?3 treated and untreated. Treatment with ?3 was by daily gavage administration of EPA and docosahexaenoic acid for 60 days. Gas chromatography was used to identify and quantify fatty acids in the blood and retina. To count lipofuscin granules and measure the photoreceptor layer, eyecups were examined histologically using transmission electron microscopy and light microscopy. We also analysed eyecups using mass spectrometry-based proteomics. Results:AA levels were lower, and EPA levels were higher, in the blood and retinas of the ?3-treated group than in the untreated group, resulting in a lower AA/EPA ratio. The ?3-treated group also showed significantly fewer lipofuscin granules and a thicker outer nuclear layer than the untreated group. Proteomic analysis revealed significantly greater expression of myelin basic protein, myelin regulatory factor-like protein, myelin proteolipid protein and glial fibrillar acidic protein in the ?3-treated group than in the untreated group. Three different pathways were significantly affected by ?3 treatment: fatty acid elongation, biosynthesis of unsaturated fatty acids and metabolic pathways. Conclusion:Two months of ?3 supplementation (when the blood AA/EPA~1.0-1.5) in aged mice reduced lipofuscin granule formation in the retina and protected the photoreceptor layer, suggesting that ?3 supplementation slows normal age-related retinal degeneration.

SUBMITTER: Prokopiou E

PROVIDER: S-EPMC6861077 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice.

Prokopiou Ekatherine E Kolovos Panagiotis P Georgiou Christos C Kalogerou Maria M Potamiti Louiza L Sokratous Kleitos K Kyriacou Kyriacos K Georgiou Tassos T

BMJ open ophthalmology 20191110 1

<h4>Objective</h4>To evaluate the therapeutic effects of omega-3 (ω3) fatty acids in the retina of aged mice when the blood arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is maintained between 1.0 and 1.5.<h4>Methods and analysis</h4>Aged (24-month-old) wild-type C57BL/6J mice were allocated to two groups: ω3 treated and untreated. Treatment with ω3 was by daily gavage administration of EPA and docosahexaenoic acid for 60 days. Gas chromatography was used to identify and quantify fatty ...[more]

PMID: 31799410

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Project description:BackgroundBile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro.MethodsThirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group). Body weights and blood lipid profiles were measured in all groups after 16 weeks of treatment. The concentrations of bile acids in bile and faeces were analysed using HPLC-MS (high-performance liquid chromatography-mass spectrometry). Gene transcription and the expression levels associated with bile acid absorption in the small intestines were determined using real-time PCR and Western blot. Ileal bile acid binding protein (I-BABP) was analysed using immunofluorescence. The effects of MCFAs on the permeability of bile acid (cholic acid, CA) in Caco-2 cell monolayers and I-BABP expression levels in Caco-2 cells treated with caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0) and oleic acid (C18:1) were determined.ResultsMice in the CR-MCT group exhibited lower body weights and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a higher HDL-C/LDL-C ratio than the CR-LCT group (P < 0.05). The concentrations of primary bile acids (primarily CA) and secondary bile acids in faeces and secondary bile acids in bile in the CR-MCT group were significantly higher than in the CR-LCT group (P < 0.05). C8:0 and C10:0 decreased the permeability of CA in Caco-2 cell monolayers. MCT/MCFAs (C8:0 and C10:0) inhibited I-BABP gene expression in the small intestines and Caco-2 cells (P < 0.05).ConclusionsMCT slowed the body weight increase and promoted the excretion of bile acids. MCT lowered serum cholesterol levels at least partially via reduction of bile acid absorption in the small intestine by inhibition of I-BABP expression. Our results provide the basis for clinical trials of MCT as a dietary supplement for lowering plasma cholesterol and reducing risk of CHD.

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Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice.

Publications

Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice.

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