Early adaptive response of the retina to a pro-diabetogenic diet: Impairment of cone response and gene expression changes in high-fructose fed rats.
The lack of plasticity of neurons to respond to dietary changes, such as high fat and high fructose diets, by modulating gene and protein expression has been associated with functional and behavioral impairments that can have detrimental consequences. The inhibition of high fat-induced rewiring of hypothalamic neurons induced obesity. Feeding rodents with high fructose is a recognized and widely used model to trigger obesity and metabolic syndrome. However the adaptive response of the retina to short term feeding with high fructose is poorly documented. We therefore aimed to characterize both the functional and gene expression changes in the neurosensory retina of Brown Norway rats fed during 3 and 8 days with a 60%-rich fructose diet (n = 16 per diet and per time point). Glucose, insulin, leptin, triacylglycerols, total cholesterol, HDL-cholesterol, LDL-cholesterol and fructosamine were quantified in plasma (n = 8 in each group). Functionality of the inner retina was studied using scotopic single flash electroretinography (n = 8 in each group) and the individual response of rod and cone photoreceptors was determined using 8.02 Hz Flicker electroretinography (n = 8 in each group). Analysis of gene expression in the neurosensory retina was performed by Affymetrix genechips, and confirmed by RT-qPCR (n = 6 in each group). Elevated glycemia (+13%), insulinemia (+83%), and leptinemia (+172%) was observed after 8 days of fructose feeding. The cone photoreceptor response was altered at day 8 in high fructose fed rats (Δ = 0.5 log unit of light stimulus intensity). Affymetrix analysis of gene expression highlighted significant modulation of the pathways of eIF2 signaling and endoplasmic reticulum stress, regulation of eIF4 and p70S6K signaling, as well as mTOR signaling and mitochondrial dysfunction. RT-qPCR analysis confirmed the down regulation of Crystallins, Npy, Nid1 and Optc genes after 3 days of fructose feeding, and up regulation of End2. Meanwhile, a trend towards an increased expression of αA- and αB-crystallin proteins was observed at day 8. Our results are consistent with early alterations of the functioning and gene expression in the retina in a pro diabetogenic environment.
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Magalie
M
Thierry
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Bruno
B
Pasquis
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Bénédicte
B
Buteau
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Cynthia
C
Fourgeux
INSERM, UMR964 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67404 Illkirch, France; CNRS, UMR7104 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67404 Illkirch, France; Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67404 Illkirch, France; IGBMC, Microarray and Sequencing Platform, F-67404 Illkirch, France.
Doulaye
D
Dembele
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Laurent
L
Leclere
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; University Hospital, Department of Clinical Chemistry, F-21000 Dijon, France.
Ségolène
S
Gambert-Nicot
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
Niyazi
N
Acar
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; University Hospital, Department of Ophthalmology, F-21000 Dijon, France.
Alain M
AM
Bron
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; University Hospital, Department of Ophthalmology, F-21000 Dijon, France.
Catherine P
CP
Creuzot-Garcher
INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye and Nutrition Research Group, F-21000 Dijon, France; CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France. Electronic address: lionel.bretillon@dijon.inra.fr.
Lionel
L
Bretillon
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D003459:Crystallins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004596:Electroretinography; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D015852:Eukaryotic Initiation Factor-2 / Q000502:physiology; D019270:Fructosamine / Q000097:blood; D005632:Fructose / Q000008:administration & dosage*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051381:Rats; D012160:Retina / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*
D001786:Blood Glucose; D003459:Crystallins; D004040:Dietary Carbohydrates; D015852:Eukaryotic Initiation Factor-2; D007328:Insulin; D020738:Leptin; D005632:Fructose; D019270:Fructosamine; D002784:Cholesterol
Diet; Electroretinography; Fructose; Gene expression; Retina