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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Med 2016 ; 22 (4): 439-45 Nephropedia Template TP
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Retinal lipid and glucose metabolism dictates angiogenesis through lipid sensor Ffar1 #MMPMID26974308
Joyal JS; Sun Y; Gantner ML; Shao Z; Evans LP; Saba N; Fredrick T; Burnim S; Kim JS; Patel G; Juan AM; Hurst CG; Hatton CJ; Cui Z; Pierce KA; Bherer P; Aguilar E; Powner MB; Vevis K; Boisvert M; Fu Z; Levy E; Fruttiger M; Packard A; Rezende FA; Maranda B; Sapieha P; Chen J; Friedlander M; Clish CB; Smith LE
Nat Med 2016[Apr]; 22 (4): 439-45 PMID26974308show ga
Tissues with high metabolic rates often use lipid as well as glucose for energy, conferring a survival advantage during feast and famine.1 Current dogma suggests that high-energy consuming photoreceptors depend on glucose.2,3 Here we show that retina also uses fatty acids (FA) ?-oxidation for energy. Moreover, we identify a lipid sensor Ffar1 that curbs glucose uptake when FA are available. Very low-density lipoprotein receptor (VLDLR), expressed in tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived FA.4,5 Vldlr is present in photoreceptors.6 In Vldlr?/? retinas, Ffar1, sensing high circulating lipid levels despite decreased FA uptake5, suppresses glucose transporter Glut1. This impaired glucose entry into photoreceptors results in a dual lipid/glucose fuel shortage and reduction in the Krebs cycle intermediate ?-ketoglutarate (KG). Low ?-KG levels promote hypoxia-induced factor-1? (Hif1a) stabilization and vascular endothelial growth factor (Vegfa) secretion by starved Vldlr?/? photoreceptors, attracting neovessels to supply fuel. These aberrant vessels invading normally avascular photoreceptors in Vldlr?/? retinas are reminiscent of retinal angiomatous proliferation (RAP), a subset of neovascular age-related macular degeneration (AMD)7, associated with high vitreous VEGF levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in neovascular AMD and other retinal diseases.