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Mouse paternal RNAs initiate a pattern of metabolic disorders in a strain-dependent manner

ABSTRACT: A wide range of animal diseases result from environmental effects, and the level of many native transcripts altered. In particular, the contribution of the noncoding RNAs (ncRNAs) is becoming widely recognized. However, the composition and degree of heritability of the signals remain unclear. Here, we performed functional assays with mouse founders with different genotypes who were raised under the same conditions and diet to follow the transfer of their phenotype of obesity/diabetes to the next generation. From the results of RNA-based microinjection assays using sperm from male mice fed a high-fat diet (HFD) injected into fertilized eggs, previous reports indicated a modulation in the expression of endogenous functional alleles, leading to an obesity/diabetes phenotype in the newly generated mice. Here, two lines (F1 B6/D2 hybrid and Dnmt2-/-) demonstrate resistance to a HFD. However, the sperm RNAs from both lines administrated in a sensitive line raised on a normal diet (ND) induce obesity and diabetes. A reversal of the obesity phenotype was a centerpiece in an obese line administered with sperm RNAs from animals raised on a ND. Our results suggest that disease changes in endogenous transcripts level due to diet variation can be reversed by RNAs. Finally, we discuss the possibility that global RNA/DNA hybrid structures within a genome can act as molecular markers for directing induced epigenetic modifications.

ORGANISM(S): Mus musculus

PROVIDER: GSE166636 | GEO | 2022/04/20

REPOSITORIES: GEO

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Project description:Obesity and diabetes associated visual impairment and vascular dysfunctions are increasing reasons for vision loss. The detailed mechanisms in these diseases are still largely unknown, but mice models have been useful to study these mechanisms and explore the detailed effects of potential compounds. Such compounds usually have antioxidant and anti-inflammatory properties. These properties are found in anthocyanins and a major source of dietary anthocyanins in Nordic diet is bilberries (European wild blueberries, Vaccinium myrtillus). In this explorative study we show results with differentially expressed genes in retina using a high-fat diet (HFD) mouse model. Our findings displayed differential regulation of genes in pathways for apoptosis, inflammation and oxidative stress, especially systemic lupus erythematosus (SLE), mitogen activated protein kinase (MAPK) and glutathione metabolism. Mice fed with HFD had increased retinal gene expression of several crystallins, which was reduced in the retina of mice fed with bilberries. Bilberries seem to reduce the expression of genes in MAPK and to increase the expression of genes in glutathione metabolism pathway. All together despite minor effects in the mouse phenotype, a diet rich in bilberries may prevent the retinal gene expression changes in the early stages of obesity. Mice were fed ad libitum with normal control diet (NCD, 10% kcal fat), high-fat diet (HFD, 45% kcal fat), 5% (w/w) freeze-dried biberries (Vaccinium myrtillus) in NCD (NCD+BB) or HFD (HFD+BB) for 12 weeks. Diets were prepared in Research Diets Inc. Feed consumption and weight gain were measured during the feeding trial, and blood pressure and serum markers of obesity at the end. Retinas were collected and RNA extracted from all 24 mice samples, and pooled retinas from 4 mice per group were hybridized with standard Illumina protocols. The expression in retinas was analyzed using R, Pathvisio and DAVID to screen for differences between high-fat and berry induced changes to control diets and further bilberry induced changes to HFD up- or downregulated transcripts. diet: NCD, HFD, NCD+BB, HFD+BB

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Mouse paternal RNAs initiate a pattern of metabolic disorders in a strain-dependent manner

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