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Bilberries potentially alleviate stress-related retinal gene expression induced by a high-fat diet in mice
Otto T Mykkänen1, Giedrius Kalesnykas, Michiel Adriaens
1Department of Clinical Nutrition, Food and Health Research Centre, University of Eastern Finland, Kuopio, Finland. otto.mykkanen@uef.fi
Purpose:
Obesity- and diabetes-associated visual impairment and vascular dysfunctions are increasing as causes of vision loss. The detailed mechanisms of how obesity and diabetes affect eye health are still largely unknown, but animal models have been useful in exploring the effects of potential protective compounds, i.e., compounds characterized by antioxidant and anti-inflammatory properties. These properties occur in anthocyanins, and bilberries (European wild blueberries, Vaccinium myrtillus) are a major source of dietary anthocyanins in Nordic diets. The main aim of the present work was to study the protective effects of dietary bilberries (BB) on the level of gene expression in retinas in mice that develop obesity when fed a high-fat diet (HFD).
Methods:
Mice (n=6 per group, four groups) were fed ad libitum a normal control diet (NCD), a HFD, or a diet with 5% bilberries (NCD+BB, HFD+BB) for 12 weeks. Food consumption, weight gain, and blood pressure were measured during the feeding period and whole blood serum markers of obesity at sacrifice. Retinas were collected, and RNA extracted from all 24 mice and pooled samples from four mice per group were hybridized to Mouse-Ref8 V2 Expression BeadChips (Illumina platform) with 25,697 probes for genes and transcript variants. The expression profiles in the retinas were analyzed using R, PathVisio, and DAVID to screen for high fat-induced changes as well as for bilberry-induced changes in the HFD up- or downregulated transcripts.
Results:
The HFD and HFD+BB groups gained weight from week 5 and final weight, blood glucose, serum free fatty acids, and systolic blood pressure as compared to mice fed the control diets (Mann-Whitney's U-test, p<0.05). Bilberries had no significant effect on these parameters other than a trend to reduce systolic blood pressure in the HFD-fed mice (101±4 versus 113±9 mmHg, p=0.10). Gene ontology enrichment analysis of 810 differentially expressed genes (F-test, p<0.05) in the retina displayed differential regulation of genes in ontology groups, mainly pathways for apoptosis, inflammation, and oxidative stress, especially systemic lupus erythematosus, mitogen-activated protein kinase, and glutathione metabolism. Mice fed a HFD had increased retinal gene expression of several crystallins, while the HFD+BB mice showed potential downregulation of these crystallins when compared to the HFD mice. Bilberries also reduced the expression of genes in the mitogen-activated protein kinase (MAPK) pathway and increased those in the glutathione metabolism pathway.
Conclusions:
HFD feeding induces differential expression of several stress-related genes in the mouse retina. Despite minor effects in the phenotype, a diet rich in bilberries mitigates the upregulation of crystallins otherwise induced by HFD. Thus, the early stages of obesity-associated and stress-related gene expression changes in the retina may be prevented with bilberries in the diet.
Insights
Dietary bilberries may protect the retina from obesity-induced stress. This study found bilberries mitigated changes in retinal gene expression related to stress and apoptosis in mice fed a high-fat diet (HFD).
Area of Science:
- Ophthalmology
- Nutritional Science
- Molecular Biology
Background:
- Obesity and diabetes are increasing causes of vision loss, linked to vascular dysfunction and visual impairment.
- Mechanisms linking obesity/diabetes to eye health are unclear, but antioxidant and anti-inflammatory compounds show promise.
- Bilberries, rich in anthocyanins, are a significant source of these beneficial compounds in Nordic diets.
Purpose of the Study:
- To investigate the protective effects of dietary bilberries (BB) on retinal gene expression in mice fed a high-fat diet (HFD).
- To understand how obesity impacts eye health at a molecular level using a mouse model.
Main Methods:
- Mice were fed normal or high-fat diets (HFD), with or without 5% bilberries, for 12 weeks.
- Retinal gene expression was analyzed using Illumina MouseRef8 V2 Expression BeadChips.
- Bioinformatic analyses (R, PathVisio, DAVID) identified differentially expressed genes and pathways.
Main Results:
- HFD induced weight gain, elevated blood glucose, free fatty acids, and blood pressure compared to controls.
- Retinal gene expression analysis revealed differential regulation in pathways for apoptosis, inflammation, and oxidative stress.
- Bilberries mitigated HFD-induced upregulation of crystallins and reduced MAPK pathway gene expression, while increasing glutathione metabolism gene expression.
Conclusions:
- High-fat diet feeding alters gene expression in the mouse retina, particularly in stress-related pathways.
- Dietary bilberries can counteract some HFD-induced gene expression changes in the retina, including crystallin upregulation.
- Bilberries may offer a dietary strategy to prevent early-stage obesity-associated retinal gene expression changes.
