Mouse
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ABSTRACT:
PROVIDER: PRJNA558801 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Excessive intake of a western diet (WD), characterized by high fat and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms through which dietary changes lead to IBD development remain unknown. Here, we generated a murine model of severe intestinal inflammation triggered by long-term WD consumption, which exhibited markedly elevated taste receptor TAS1R3 expression in inflamed bowel tissues. Thus, we hypothesized that nutrient-induced TAS1R3 modulation is central to regulating intestinal inflammation. We tested our hypothesis by analyzing changes in gene expression profiles and inflammatory cell infiltration in the inflamed bowel tissues of WD-fed Tas1r3-deficient mice. Methods: We carried out RNA-Seq of ileum tissue of wild-type (WT) and taste receptor Tas1r3 knockout (Tas1r3−/−) mice fed a normal diet (ND) or western diet (WD) for 10 weeks using Ion Proton System. Raw RNA-seq reads were split into individual samples based on barcodes and quality controlled using the FASTQC tool. The reads were analyzed with Partek Flow software (Partek, St. Louis, MI, USA) (http://www.partek.com/partekgs). The sequence reads that passed quality filters were analyzed at the transcript isoform level. Results: We confirmed that Tas1r3-deficient mice are protected from WD-induced intestinal inflammation. Consistent with little or no phenotypic change in the ND group, the gene expression profiles from the ND-fed Tas1r3−/− and WT mice were similar, whereas the ileal transcriptome profiles from the WD-fed Tas1r3−/− mice were readily distinguishable from those of WD-fed WT mice. Inflammatory cytokines such as Tnfα and Il1b were highly expressed in WD-fed WT mice, whereas Pparg, Tjp3, and Defa27 were highly expressed in WD-fed Tas1r3−/− mice. Importantly, we confirmed that the absence of TAS1R3 caused a significant reduction in the inflammatory response-related signaling pathway; GSEA plots also revealed that the mTOR signaling pathway was greatly suppressed. Most notably, the PPAR signaling pathway was significantly affected by TAS1R3 absence. GSEA confirmed that genes associated with the PPAR signaling pathway were significantly enriched in the set of DEGs between Tas1r3−/− and WT mice in the WD groups. Conclusion: Our data suggest that, due to its suppressive action on mTOR, TAS1R3 might function as an important regulator of the PPAR-γ signaling pathway in the intestinal tract.
2023-04-19 | GSE190059 | GEO
Project description:Wildtype (WT) and albumin-knockout (AKO) were fed with normal diet. We harvested the liver tissues from WT and AKO mice at 3-week, 8-week, and 10-month of age. We then performed gene expression profiling analysis using data obtained from RNA-seq of the six different liver tissues. Wildtype (WT) and albumin-knockout (AKO) mice were fed with Normal diet (ND) or Western diet (WD) for 8 weeks from the age of 8 weeks. We harvested the liver tissues from WT-ND, WT-WD, AKO-ND, AKO-WD mice . We then performed gene expression profiling analysis using data obtained from RNA-seq of the four different liver tissues. Wildtype (WT) mice fed with HFD from the age of 8 weeks were injected by 17-AAG at the 3rd, 4th, 5th, 6.5th, and 8th weeks of the HFD feeding process. The control group was injected by the solvent. Another group of mice at the same age was fed with normal diet (ND). We harvested the liver tissues ND, Ctrl, and 17-AAG mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of the three different liver tissues.
2023-01-20 | GSE222922 | GEO
Project description:Accumulating studies support that the western diet (WD), a diet comprised of saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety, remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) is identified in the hypothalamus, a key brain area involved in both sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the role of the hypothalamic TAS1R3 in WD-induced anxiety using wild-type (WT) and Tas1r3 deficient (Tas1r3-/-) mice fed a normal diet (ND) or WD for 12 weeks. We evaluated anxiety levels with the open field test and the elevated plus maze test. Behavior tests showed WD increased anxiety in WT mice, whereas Tas1r3-/- mice were protected from WD-induced anxiety. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3-/- mice, we found 1,437 genes significantly regulated by Tas1r3 deficiency. In addition, bioinformatic analysis revealed that CREB-mediated maintenance of neuronal regeneration, which can prevent the development of anxiety, was enhanced in WD-fed Tas1r3-/- mice compared to WD-fed WT mice. In addition, in vitro studies further confirmed that Tas1r3 knockdown prevented suppression of CREB caused by high levels of glucose, fructose, and palmitic acid in adult hypothalamic neuronal cells. These results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of the WD on anxiety.
2023-08-05 | GSE216063 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is a sexually dimorphic disease influenced by dietary factors. Here, we assess the metabolic and hepatic effects of dietary amino acid (AA) source in Western diet (WD)-induced NAFLD in male and female mice. The AA source was either casein or a free AA mixture mimicking the composition of casein. As expected, males fed a casein-based WD displayed glucose intolerance, fasting hyperglycemia, and insulin-resistance and developed NAFLD associated with changes in hepatic gene expression and dysbiosis. In contrast, males fed the AA-based WD showed no steatosis, a similar gene expression profile as males fed a control diet, and a distinct microbiota composition compared to males fed a casein-based WD. Females were protected against WD-induced liver damage, hepatic gene expression, and gut microbiota changes regardless of the AA source. Thus, free dietary AA intake prevents the unhealthy metabolic outcomes of a WD in a sex-specific manner.
2024-01-01 | GSE234591 | GEO
Project description:The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.
2019-12-31 | GSE104914 | GEO
Project description:The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was deployed on jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon. There was also a significant effect of the WD on the gut proteome. A significant reduction was detected in Paneth cell proteins with anti-microbial activity, including lysozyme C-1, angiogenin-4, cryptdin-related sequence1C-3 and -2, a-defensin 17 and intelectin-1a. The key protein expressed by goblet cells, mucin-2, was also reduced in the IE-irKO mice. Proteins involved in lipid metabolism, including aldose reductase-related protein 1, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], apolipoprotein A-II and pyruvate dehydrogenase kinase isozyme 4, were increased in the mucosa of WD-fed IE-irKO mice as compared to controls. In contrast, expression of the nutrient-responsive gut hormones, glucose-dependent insulinotropic polypeptide and neurotensin, was reduced in the jejunal mucosa of IE-irKO mice, and there was a reduction in proteins of the P-type ATPases and the solute carrier-transporter family in the colon of WD-fed IE-irKO mice. In conclusion, IE-irKO mice display a distinct molecular phenotype, suggesting a biological role of insulin and its receptor in determining differentiated cell-specificity in the intestinal epithelium.
2017-08-18 | PXD005932 | Pride
Project description:Morus alba L. Raw protein sequence reads and sequence
2024-02-08 | PXD049451 | iProX
Project description:The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.
2019-12-31 | GSE104913 | GEO