Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration
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2013-01-01
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Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT1, eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. © 2012 John Wiley & Sons, Ltd.
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AKT , Cell death , High-fat diet , Insulin resistance , Lipid peroxidation , NOS isoforms , Obesity , Retina , 4 hydroxynonenal , endothelial nitric oxide synthase , inducible nitric oxide synthase , insulin receptor substrate , neuronal nitric oxide synthase , nitric oxide synthase , phosphatidylinositol 3 kinase , protein kinase B , animal experiment , animal model , apoptosis , controlled study , diabetic retinopathy , immunoblotting , immunohistochemistry , insulin resistance , intracellular signaling , lipid diet , male , nonhuman , obesity , priority journal , protein expression , rat , retina , retina degeneration , Animals , Apoptosis , Astrocytes , Blood Glucose , Diabetic Retinopathy , Dietary Fats , Disease Models, Animal , Eye Proteins , Fatty Acids , Insulin Receptor Substrate Proteins , Insulin Resistance , Lipid Peroxidation , Lipids , Liver , Male , Nitric Oxide Synthase Type I , Nitric Oxide Synthase Type III , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Rats , Rats, Wistar , Retinal Degeneration , Signal Transduction , Animalia , Rattus
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Cell Biochemistry and Function, v. 31, n. 1, p. 65-74, 2013.