Remodeling of Retinal Fatty Acids in an Animal Model of Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 1; pp. 219 - 227
• Main Authors: Tikhonenko, Maria, Lydic, Todd A., Wang, Yun, Chen, Weiqin, Opreanu, Madalina, Sochacki, Andrew, McSorley, Kelly M., Renis, Rebecca L., Kern, Timothy, Jump, Donald B., Reid, Gavin E., Busik, Julia V.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.01.2010
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db09-0728

Remodeling of Retinal Fatty Acids in an Animal Model of Diabetes A Decrease in Long-Chain Polyunsaturated Fatty Acids Is Associated With a Decrease in Fatty Acid Elongases Elovl2 and Elovl4 Maria Tikhonenko 1 , Todd A. Lydic 1 , Yun Wang 2 , Weiqin Chen 3 , Madalina Opreanu 1 , 4 , Andrew Sochacki 1 , Kelly M. McSorley 1 , Rebecca L. Renis 5 , Timothy Kern 6 , Donald B. Jump 7 , Gavin E. Reid 5 , 8 and Julia V. Busik 1 1 Department of Physiology, Michigan State University, East Lansing, Michigan; 2 GTx, Memphis, Tennessee; 3 Department of Medicine, Baylor College of Medicine, Houston, Texas; 4 Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan; 5 Department of Chemistry, Michigan State University, East Lansing, Michigan; 6 Department of Medicine, Division of Endocrinology, Case Western Reserve University, Cleveland, Ohio; 7 Linus Pauling Institute, Oregon State University, Corvallis, Oregon; 8 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan. Corresponding author: Julia V. Busik, busik{at}msu.edu . M.T. and T.A.L. contributed equally to this work. 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. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received June 4, 2009. Accepted September 9, 2009. © 2010 American Diabetes Association