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Transcriptomic changes upon ESRRA loss in the small intestinal epithelium

ABSTRACT: Amidst the obesity epidemic and advancements in satiety-targeting therapies, the transcriptional control of energy metabolism is crucial for managing obesity. The transcription factor Estrogen-related receptor α (ESRRA) regulates genes involved in mitochondrial biogenesis, gluconeogenesis, oxidative phosphorylation, and fatty acid metabolism. Although not essential for basic cellular function, ESRRA is vital for energy supply during physiological and pathological challenges. Studies show Esrra mutant mice have impaired fat metabolism and absorption, with germline Esrra loss conferring resistance to high-fat diet (HFD)-induced obesity. However, these studies often overlook tissue-specific roles. Esrra knockdown in the medial pre-frontal cortex reduces feeding and HFD-induced obesity, indicating possible neurological involvement. Notably, ESRRA is highly expressed in the gastrointestinal (GI) tract, a key player in dietary lipid metabolism and target of weight loss therapies.This study aims to investigate the impact of intestinal ESRRA and determine whether it contributes to resistance to diet-induced obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE269825 | GEO | 2024/07/10

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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Transcriptomic changes upon ESRRA loss in the small intestinal epithelium

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