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, Todd A. Lydic, Yun Wang, Weiqin Chen, Madalina Opreanu, Andrew Sochacki, Kelly M. McSorley, Rebecca L. Renis, Timothy Kern, Donald B. Jump, Gavin E. Reid, Julia V. Busik

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalDiabetes
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2010

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Unsaturated Fatty Acids
Fatty Acids
Animal Models
Retina
Diabetes Complications
Liver
Gene Expression
Electrospray Ionization Mass Spectrometry
Docosahexaenoic Acids
Omega-3 Fatty Acids
Diabetic Retinopathy
Reverse-Phase Chromatography
Intercellular Adhesion Molecule-1
Streptozocin
Dyslipidemias
Tandem Mass Spectrometry
Phosphatidylcholines
Transcriptome
Vascular Endothelial Growth Factor A
Interleukin-6

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / 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.

In: Diabetes, Vol. 59, No. 1, 01.01.2010, p. 219-227.

Research output: Contribution to journalArticle

Tikhonenko, M, Lydic, TA, Wang, Y, Chen, W, Opreanu, M, Sochacki, A, McSorley, KM, Renis, RL, Kern, T, Jump, DB, Reid, GE & Busik, JV 2010, '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', Diabetes, vol. 59, no. 1, pp. 219-227. https://doi.org/10.2337/db09-0728
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. / 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. In: Diabetes. 2010 ; Vol. 59, No. 1. pp. 219-227.
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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.",
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T2 - A decrease in long-chain polyunsaturated fatty acids is associated with a decrease in fatty acid elongases Elovl2 and Elovl4

AU - Tikhonenko, Maria

AU - Lydic, Todd A.

AU - Wang, Yun

AU - Chen, Weiqin

AU - Opreanu, Madalina

AU - Sochacki, Andrew

AU - McSorley, Kelly M.

AU - Renis, Rebecca L.

AU - Kern, Timothy

AU - Jump, Donald B.

AU - Reid, Gavin E.

AU - Busik, Julia V.

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N2 - 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.

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