Remodeling of Retinal Fatty Acids in an Animal Model of Diabetes
Open Access
- 29 October 2009
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 59 (1), 219-227
- https://doi.org/10.2337/db09-0728
Abstract
OBJECTIVE: The results of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort study revealed a strong association between dyslipidemia and the development of diabetic retinopathy. However, there are no experimental data on retinal fatty acid metabolism in diabetes. This study determined retinal-specific fatty acid metabolism in control and diabetic animals. RESEARCH DESIGN AND METHODS: Tissue gene and protein expression profiles were determined by quantitative RT-PCR and Western blot in control and streptozotocin-induced diabetic rats at 3–6 weeks of diabetes. Fatty acid profiles were assessed by reverse-phase high-performance liquid chromatography, and phospholipid analysis was performed by nano-electrospray ionization tandem mass spectrometry. RESULTS: We found a dramatic difference between retinal and liver elongase and desaturase profiles with high elongase and low desaturase gene expression in the retina compared with liver. Elovl4, an elongase expressed in the retina but not in the liver, showed the greatest expression level among retinal elongases, followed by Elovl2, Elovl1, and Elovl6. Importantly, early-stage diabetes induced a marked decrease in retinal expression levels of Elovl4, Elovl2, and Elovl6. Diabetes-induced downregulation of retinal elongases translated into a significant decrease in total retinal docosahexaenoic acid, as well as decreased incorporation of very-long-chain polyunsaturated fatty acids (PUFAs), particularly 32:6n3, into retinal phosphatidylcholine. This decrease in n3 PUFAs was coupled with inflammatory status in diabetic retina, reflected by an increase in gene expression of proinflammatory markers interleukin-6, vascular endothelial growth factor, and intercellular adhesion molecule-1. CONCLUSIONS: This is the first comprehensive study demonstrating diabetes-induced changes in retinal fatty acid metabolism. Normalization of retinal fatty acid levels by dietary means or/and modulating expression of elongases could represent a potential therapeutic target for diabetes-induced retinal inflammation.Keywords
This publication has 49 references indexed in Scilit:
- Electron Impact Mass Spectroscopic Studies on Mouse Retinal Fatty AcidsOphthalmic Research, 2009
- Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acidsProceedings of the National Academy of Sciences, 2008
- Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesityJournal of Lipid Research, 2006
- Effect of docosahexaenoic acid intake on lipid peroxidation in diabetic rat retina under oxidative stressFree Radical Research, 2006
- Influence of Plasma Free Fatty Acids on Lipoprotein Synthesis and Diabetic DyslipidemiaExperimental and Clinical Endocrinology & Diabetes, 2003
- Gene regulation of mammalian desaturasesBiochemical Society Transactions, 2002
- Enhanced Expression of Adhesion Molecules of the Retinal Vascular Endothelium in Spontaneous Diabetic RatsOphthalmic Research, 2002
- Is diabetic retinopathy an inflammatory disease?British Journal of Ophthalmology, 2002
- Nonsteroidal anti‐inflammatory drugs prevent early diabetic retinopathy via TNF‐α suppressionThe FASEB Journal, 2002
- Effects of Diabetes and Insulin on Hepatic Δ6 Desaturase Gene ExpressionBiochemical and Biophysical Research Communications, 2001