Effects of Diets with Different Proportions of Protein/Carbohydrate on Retinal Manifestations in db Mice

Abstract

Background/aim: Diabetic nephropathy is aggravated by a higher intake of total protein. The effects of diets with different proportions of protein and carbohydrate on diabetic retinopathy in db mice, a type-2 diabetes animal model, were examined, as well as diabetic nephropathy.

Materials and methods: Control and db mice at 5 weeks of age were fed the diets (% energy of protein/carbohydrate/fat; L-diet: 12/71/17; H-diet: 24/59/17) under ad libitum conditions and pair-feeding conditions for 6 weeks, respectively.

Results: Mice fed the H-diet showed significantly greater retinal thickness by optical coherence tomography, and lower mRNA levels of angiotensinogen. Comparing combinations of diets and genotypes, db-H mice showed significantly higher mRNA levels of angiotensin-converting enzyme, advanced glycosylation end product-specific receptor, and cluster of differentiation molecule 11b (a microglial marker) than db-L mice.

Conclusion: Dietary protein and carbohydrate proportions influenced retinal manifestations, including retinal thickness and gene expression in control and diabetic mice.

Keywords: db Mice; diabetic retinopathy; optical coherence tomography; renin-angiotensin system.

Figure 1. Change of body weight and water intake in control (CT) and db mice with different diet conditions. Body weight (A) and water intake (B) of CT (open symbol) and db (closed symbol) mice fed with the different diets (low protein: triangle, high protein: circle) for 6 weeks. The total amounts of food eaten by CT (open symbol) and db (closed symbol) mice fed with a low protein diet (L) or a high protein diet (H) are shown in (C). The data are presented as means+SE from six db and six CT mice under the different diet conditions. Data were analyzed statistically by two-way ANOVA (repeated measurements) (A and B) or unpaired t-test (C). *p<0.05 compared to CT mice fed with the respective diet

Figure 2. Messenger RNA levels of genes related to the renin-angiotensin system, diabetic conditions, and of neuronal and glial marker genes.Messenger RNA levels of Agt (A), Ace (B), Ager (C), NeuN (D), Gfap (E), and CD11b (F) in control (CT, open symbol) and db (closed symbol)mice fed with a low protein diet (L) or a high protein diet (H) at 11 weeks of age. The data are presented as means+SE from six db and six CT mice under the respective conditions. The p-values from two-way ANOVA (two factors: diet and genotype) are shown at the left and upper portion of each figure. Diet x Genotype means the interaction between diet and genotype. The level of gene expression in CT-L mice was set at 1.0 using Gapdh as a reference gene. The data were analyzed statistically by the unpaired t-test. *p<0.05 compared with CT mice fed with the respective diet. #p<0.05 compared to the same genotype mice fed the L diet.