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Aruna Gorusupudi, Fu-Yen Chang, Kelly Nelson, Gregory S Hageman, Paul S Bernstein; Supplementation with n3 Fatty Acids to Improve VLC-PUFA Levels in Diabetic Animal Models. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2665.
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The main causative factors for diabetic retinopathy are hyperglycemia and dyslipidemia. Decreased serum n3/n6 ratios (omega-3 index) observed in diabetic patients are indicative of chronic inflammation and could be a contributing factor for diabetic retinopathy. n3 fatty acids are not only biologically active molecules, but they also give rise to other biologically active non-dietary molecules such as very long chain-polyunsaturated fatty acids (VLC-PUFAs) and neuroprotectins which can play major roles in pathological processes. VLC-PUFAs are a special class of fatty acids present only in the vertebrate retina that are responsible for membrane fluidity in the photoreceptors. We observed a significant drop in VLC-PUFA levels and alterations to their n3/n6 ratios in retinal punches from patients with diabetic retinopathy, compared to those of diabetic and age-matched controls. We chose to study the effect of n-3 PUFA supplementation on VLC-PUFA levels in two spontaneous diabetic models: heterozygous Ins2Akita (Akita) mice and Nile grass rats. We hypothesize that treatment with VLC-PUFA precursor n3 fatty acids could improve serum adiponectin levels and omega-3 index and retinal n3/n6 VLC-PUFA ratios and levels, thereby slowing retinopathy.
Akita and WT (C57B6L) mice (n=6/group) were fed with custom formulated fish oil (2:1v/v, 1.2 g/kg/day) diet for eight weeks. Diabetic Nile grass rats, were fed with fish oil mixed with pellet diet for 8 weeks. Animals were sacrificed, and serum, liver, brain and eye tissues were harvested. Retinas were separated from RPE and used for VLC-PUFA analysis. Using a standardized method, fatty acid methyl esters were extracted and then analyzed by GC-MS.
After two months of supplementation with n-3 PUFA rich fish oil, there was a significant increase in n-3/n-6 VLC-PUFA ratios in both models compared to diabetic controls who were not fed fish oil. We also observed a decrease in serum blood glucose and an increase in serum adiponectin levels. The fish oil supplemented Akita mice had lower adiponectin levels when compared to control Akita mice.
Our results indicate that VLC-PUFA levels were lower in diabetes and diabetic retinopathy, suggesting that dietary supplementation with n3 LC-PUFAs may help to prevent progression of diabetes and associated retinopathy
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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