Wild blueberries (Vaccinium myrtillus) alleviate inflammation and hypertension associated with developing obesity in mice fed with a high-fat diet.

BACKGROUND: Low-grade metabolic inflammation and hypertension are primary mechanisms involved in obesity-associated adverse health effects. Berries, especially Nordic wild blueberries (hereafter referred to as bilberries), represent an important source of dietary anthocyanins, a group of polyphenols with potential beneficial effects to combat obesity-associated metabolic disturbances. METHODS: The effects of 5% or 10% (w/w) of whole bilberries (BB) were studied on the development of obesity and its metabolic disturbances in C57BL mice fed with a high-fat diet (HFD) for three months. Cytokines, inflammatory cells, systolic blood pressure, glucose tolerance, insulin sensitivity, weight gain, body fat, food consumption and energy metabolism were assessed. RESULTS: Bilberries ameliorated type 1 pro-inflammatory responsiveness induced by HFD. This was indicated by the altered cytokine profile and the reduced prevalence of interferon gamma -producing T-cells, in particular T helper type 1 cells. Bilberries also prevented the progression of obesity associated long term increase in systolic blood pressure in mice. CONCLUSIONS: Bilberries reduce the development of systemic inflammation and prevent the progression of chronic hypertension, thus supporting their potential role in alleviating the adverse health effects associated with developing obesity.

Bilberries potentially alleviate stress-related retinal gene expression induced by a high-fat diet in mice.

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.