Skip to main content
Top
Published in: Inflammation 3/2020

01-06-2020 | Original Article

Evidence on n-3 Fatty Acids and Oleic Acid Role in Retinal Inflammation and Microvascular Integrity: Insight from a Hyperlipidemic Rat Model

Authors: Sadashivaiah Bettadahalli, Pooja Acharya, Ramaprasad Talahalli

Published in: Inflammation | Issue 3/2020

Login to get access

Abstract

Loss of retinal function due to manifestation of chronic inflammation and oxidative stress in hyperglycemia is well addressed. However, the effect of hyperlipidemia on retinal inflammation and microvascular integrity, and the modulatory effects of oxidation-stable oleic acid and long-chain n-3 fatty acids have never been addressed. The objective of this investigation was to assess the retinoprotective effect of oxidation stable oleic acid and oxidation-susceptible EPA + DHA on retinal inflammation and microvascular integrity, under hyperlipidemic conditions. Male Wistar rats were fed with control (7.0% lard), high-fat (35.0% lard), high-fat with fish oil (17.5% fish oil + 17.5% lard), high-fat with olive oil (17.5% olive oil + 17.5% lard), and high-fat with fish oil and olive oil (11.66% fish oil + 11.66% of olive oil + 11.66% of lard) diet for 90 days. Systemic and retinal inflammation, as measured by eicosanoids and cytokines, retinal expression of NF-kB, capillary degeneration, and pericyte loss, were assessed. Hyperlipidemia significantly (p < 0.05) increased the markers of inflammation (PGE2, LTB4, LTC4, IL-1β, MCP-1, and TNF-α) in serum and retina. Besides, the retinal NF-kB-p65 expression, capillary degeneration, and pericyte loss were significantly (p < 0.05) increased under hyperlipidemic conditions. Dietary incorporation of oleic acid and EPA + DHA significantly (p < 0.05) suppressed hyperlipidemia-induced effects in the retina. In conclusion, hyperlipidemia causes retinal aberrations by compromising the balance in the inflammatory response and microvascular integrity. Dietary incorporation of oleic acid and long-chain n-3 fatty acids prevents hyperlipidemia-induced aberrations in the retina.
Literature
1.
go back to reference Stem, M.S., and T.W. Gardner. 2013. Neurodegeneration in the pathogenesis of diabetic retinopathy: Molecular mechanisms and therapeutic implications. Current Medicinal Chemistry 20: 3241–3250.CrossRef Stem, M.S., and T.W. Gardner. 2013. Neurodegeneration in the pathogenesis of diabetic retinopathy: Molecular mechanisms and therapeutic implications. Current Medicinal Chemistry 20: 3241–3250.CrossRef
2.
go back to reference Hardy, P., M. Beauchamp, F. Sennlaub, F. Gobeil Jr., L. Tremblay, B. Mwaikambo, P. Lachapelle, and S. Chemtob. 2005. New insights into the retinal circulation: Inflammatory lipid mediators in ischemic retinopathy. Prostaglandins, Leukotrienes and Essential Fatty Acids 72: 301–325.CrossRef Hardy, P., M. Beauchamp, F. Sennlaub, F. Gobeil Jr., L. Tremblay, B. Mwaikambo, P. Lachapelle, and S. Chemtob. 2005. New insights into the retinal circulation: Inflammatory lipid mediators in ischemic retinopathy. Prostaglandins, Leukotrienes and Essential Fatty Acids 72: 301–325.CrossRef
3.
go back to reference Gubitosi-Klug, R.A., R. Talahalli, Y. Du, J.L. Nadler, and T.S. Kern. 2008. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes 57: 1387–1393.CrossRef Gubitosi-Klug, R.A., R. Talahalli, Y. Du, J.L. Nadler, and T.S. Kern. 2008. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes 57: 1387–1393.CrossRef
4.
go back to reference Talahalli, R.R., S. Zarini, J. Tang, G. Li, R. Murphy, T.S. Kern, and R.A. Gubitosi-Klug. 2013. Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes. Journal of Leukocyte Biology 93: 135–143.CrossRef Talahalli, R.R., S. Zarini, J. Tang, G. Li, R. Murphy, T.S. Kern, and R.A. Gubitosi-Klug. 2013. Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes. Journal of Leukocyte Biology 93: 135–143.CrossRef
5.
go back to reference Rader, D.J. 2007. Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. The American Journal of Medicine 120: S12–S18.CrossRef Rader, D.J. 2007. Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. The American Journal of Medicine 120: S12–S18.CrossRef
6.
go back to reference Ramaiyan, B., S. Bettadahalli, and R.R. Talahalli. 2016. Dietary omega-3 but not omega-6 fatty acids down-regulate maternal dyslipidemia induced oxidative stress: A three generation study in rats. Biochemical and Biophysical Research Communications 477: 887–894.CrossRef Ramaiyan, B., S. Bettadahalli, and R.R. Talahalli. 2016. Dietary omega-3 but not omega-6 fatty acids down-regulate maternal dyslipidemia induced oxidative stress: A three generation study in rats. Biochemical and Biophysical Research Communications 477: 887–894.CrossRef
7.
go back to reference Ramaiyan, B., and R.R. Talahalli. 2018. Dietary n-3 but not n-6 fatty acids down-regulate maternal dyslipidemia induced inflammation: A three-generation study in rats. Prostaglandins, Leukotrienes and Essential Fatty Acids 135: 83–91.CrossRef Ramaiyan, B., and R.R. Talahalli. 2018. Dietary n-3 but not n-6 fatty acids down-regulate maternal dyslipidemia induced inflammation: A three-generation study in rats. Prostaglandins, Leukotrienes and Essential Fatty Acids 135: 83–91.CrossRef
8.
go back to reference Acharya, P., and R.R. Talahalli. 2019. Aging and hyperglycemia intensify dyslipidemia-induced oxidative stress and inflammation in rats: Assessment of restorative potentials of ALA and EPA+ DHA. Inflammation 42: 946–952.CrossRef Acharya, P., and R.R. Talahalli. 2019. Aging and hyperglycemia intensify dyslipidemia-induced oxidative stress and inflammation in rats: Assessment of restorative potentials of ALA and EPA+ DHA. Inflammation 42: 946–952.CrossRef
9.
go back to reference Davey, R.A., N.C. Tebbutt, J.N. Favaloro, D.N. O'neal, D. Rae, J.D. Zajac, and J.D. Best. 2006. Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with type 2 diabetes mellitus. Lipids in Health and Disease 5: 29.CrossRef Davey, R.A., N.C. Tebbutt, J.N. Favaloro, D.N. O'neal, D. Rae, J.D. Zajac, and J.D. Best. 2006. Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with type 2 diabetes mellitus. Lipids in Health and Disease 5: 29.CrossRef
10.
go back to reference Calder, P.C. 2017. Omega-3 fatty acids and inflammatory processes: From molecules to man. Biochemical Society Transactions 45: 1105–1115.CrossRef Calder, P.C. 2017. Omega-3 fatty acids and inflammatory processes: From molecules to man. Biochemical Society Transactions 45: 1105–1115.CrossRef
11.
go back to reference Widmer, R.J., A.J. Flammer, L.O. Lerman, A. Lerman, and A. 2015. The Mediterranean diet, its components, and cardiovascular disease. The American Journal of Medicine 128: 229–238.CrossRef Widmer, R.J., A.J. Flammer, L.O. Lerman, A. Lerman, and A. 2015. The Mediterranean diet, its components, and cardiovascular disease. The American Journal of Medicine 128: 229–238.CrossRef
12.
go back to reference Komprda, T. 2012. Eicosapentaenoic and docosahexaenoic acids as inflammation-modulating and lipid homeostasis influencing nutraceuticals: A review. Journal of Functional Foods 4: 25–38.CrossRef Komprda, T. 2012. Eicosapentaenoic and docosahexaenoic acids as inflammation-modulating and lipid homeostasis influencing nutraceuticals: A review. Journal of Functional Foods 4: 25–38.CrossRef
13.
go back to reference Calder, P.C. 2013. n-3 fatty acids, inflammation and immunity: New mechanisms to explain old actions. Proceedings of the Nutrition Society 72: 326–336.CrossRef Calder, P.C. 2013. n-3 fatty acids, inflammation and immunity: New mechanisms to explain old actions. Proceedings of the Nutrition Society 72: 326–336.CrossRef
14.
go back to reference Anonymous. 1977. Report of the American Institute of Nutrition ad hoc Committee on Standards for Nutritional Studies. Journal of Nutrition 107: 1340–1348.CrossRef Anonymous. 1977. Report of the American Institute of Nutrition ad hoc Committee on Standards for Nutritional Studies. Journal of Nutrition 107: 1340–1348.CrossRef
15.
go back to reference Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193: 265–275.PubMed Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193: 265–275.PubMed
16.
go back to reference Tang, J., and T.S. Kern. 2011. Inflammation in diabetic retinopathy. Progress in Retinal and Eye Research 30: 343–358.CrossRef Tang, J., and T.S. Kern. 2011. Inflammation in diabetic retinopathy. Progress in Retinal and Eye Research 30: 343–358.CrossRef
17.
go back to reference Zhang, W., H. Liu, M. Al-Shabrawey, R.W. Caldwell, and R.B. Caldwell. 2011. Inflammation and diabetic retinal microvascular complications. Journal of Cardiovascular Disease Research 2: 96–103.CrossRef Zhang, W., H. Liu, M. Al-Shabrawey, R.W. Caldwell, and R.B. Caldwell. 2011. Inflammation and diabetic retinal microvascular complications. Journal of Cardiovascular Disease Research 2: 96–103.CrossRef
18.
go back to reference Gustavsson, C., C.D. Agardh, A.V. Zetterqvist, J. Nilsson, E. Agardh, and M.F. Gomez. 2010. Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia. PLoS One 5: 12699.CrossRef Gustavsson, C., C.D. Agardh, A.V. Zetterqvist, J. Nilsson, E. Agardh, and M.F. Gomez. 2010. Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia. PLoS One 5: 12699.CrossRef
19.
go back to reference Arjamaa, O., V. Aaltonen, N. Piippo, T. Csont, G. Petrovski, K. Kaarniranta, and A. Kauppinen. 2017. Hypoxia and inflammation in the release of VEGF and interleukins from human retinal pigment epithelial cells. Graefe’s Archive for Clinical and Experimental Ophthalmology 255: 1757–1762.CrossRef Arjamaa, O., V. Aaltonen, N. Piippo, T. Csont, G. Petrovski, K. Kaarniranta, and A. Kauppinen. 2017. Hypoxia and inflammation in the release of VEGF and interleukins from human retinal pigment epithelial cells. Graefe’s Archive for Clinical and Experimental Ophthalmology 255: 1757–1762.CrossRef
20.
go back to reference Bazinet, R.P., and S. Layé. 2014. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Reviews Neuroscience 15: 771.CrossRef Bazinet, R.P., and S. Layé. 2014. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Reviews Neuroscience 15: 771.CrossRef
21.
go back to reference Das, U.N. 2013. Lipoxins, resolvins, and protectins in the prevention and treatment of diabetic macular edema and retinopathy. Nutrition 29: 1–7.CrossRef Das, U.N. 2013. Lipoxins, resolvins, and protectins in the prevention and treatment of diabetic macular edema and retinopathy. Nutrition 29: 1–7.CrossRef
22.
go back to reference Calder, P.C. 2012. Mechanisms of action of (n-3) fatty acids. The Journal of Nutrition 142: 592S–599S.CrossRef Calder, P.C. 2012. Mechanisms of action of (n-3) fatty acids. The Journal of Nutrition 142: 592S–599S.CrossRef
23.
go back to reference Lugrin, J., N. Rosenblatt-Velin, R. Parapanov, and L. Liaudet. 2014. The role of oxidative stress during inflammatory processes. Biological Chemistry 395: 203–230.CrossRef Lugrin, J., N. Rosenblatt-Velin, R. Parapanov, and L. Liaudet. 2014. The role of oxidative stress during inflammatory processes. Biological Chemistry 395: 203–230.CrossRef
24.
go back to reference Li, Y., D. Chen, L. Sun, Y. Wu, Y. Zou, C. Liang, Y. Bao, J. Yi, Y. Zhang, J. Hou, and Z. Li. 2019. Induced expression of VEGFC, ANGPT, and EFNB2 and their receptors characterizes neovascularization in proliferative diabetic retinopathy. Investigative Ophthalmology & Visual Science 60: 4084–4096.CrossRef Li, Y., D. Chen, L. Sun, Y. Wu, Y. Zou, C. Liang, Y. Bao, J. Yi, Y. Zhang, J. Hou, and Z. Li. 2019. Induced expression of VEGFC, ANGPT, and EFNB2 and their receptors characterizes neovascularization in proliferative diabetic retinopathy. Investigative Ophthalmology & Visual Science 60: 4084–4096.CrossRef
25.
go back to reference Kowluru, R.A., M. Mishra, A. Kowluru, and B. Kumar. 2016. Hyperlipidemia and the development of diabetic retinopathy: Comparison between type 1 and type 2 animal models. Metabolism 65: 1570–1581.CrossRef Kowluru, R.A., M. Mishra, A. Kowluru, and B. Kumar. 2016. Hyperlipidemia and the development of diabetic retinopathy: Comparison between type 1 and type 2 animal models. Metabolism 65: 1570–1581.CrossRef
26.
go back to reference Connor, K.M., J.P. SanGiovanni, C. Lofqvist, C.M. Aderman, J. Chen, A. Higuchi, S. Hong, E.A. Pravda, S. Majchrzak, D. Carper, and A. Hellstrom. 2007. Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nature Medicine 13: 868.CrossRef Connor, K.M., J.P. SanGiovanni, C. Lofqvist, C.M. Aderman, J. Chen, A. Higuchi, S. Hong, E.A. Pravda, S. Majchrzak, D. Carper, and A. Hellstrom. 2007. Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nature Medicine 13: 868.CrossRef
27.
go back to reference Lamers, D., R. Schlich, S. Greulich, A. Sasson, H. Sell, and J. Eckel. 2011. Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells. Journal of Cellular and Molecular Medicine. 15: 1177–1188.CrossRef Lamers, D., R. Schlich, S. Greulich, A. Sasson, H. Sell, and J. Eckel. 2011. Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells. Journal of Cellular and Molecular Medicine. 15: 1177–1188.CrossRef
28.
go back to reference Tu, W., H. Wang, S. Li, Q. Liu, and H. Sha. 2019. The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging and Disease 10: 637.CrossRef Tu, W., H. Wang, S. Li, Q. Liu, and H. Sha. 2019. The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging and Disease 10: 637.CrossRef
29.
go back to reference Liu, T., L. Zhang, D. Joo, and S.C. Sun. 2017. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2: 17023.CrossRef Liu, T., L. Zhang, D. Joo, and S.C. Sun. 2017. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2: 17023.CrossRef
Metadata
Title
Evidence on n-3 Fatty Acids and Oleic Acid Role in Retinal Inflammation and Microvascular Integrity: Insight from a Hyperlipidemic Rat Model
Authors
Sadashivaiah Bettadahalli
Pooja Acharya
Ramaprasad Talahalli
Publication date
01-06-2020
Publisher
Springer US
Published in
Inflammation / Issue 3/2020
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-019-01172-1

Other articles of this Issue 3/2020

Inflammation 3/2020 Go to the issue