Proteomics of ACF as they mature and transform into intestinal adenomas
Ontology highlight
ABSTRACT: Proteomics of ACF as they mature and transform into intestinal adenomas in an AOM murine model consuming a normal diet under normal conditions.
Project description:Steatohepatitis progresses to cancer via immunosuppression of HCC directed CD8+ T cells
LC/MS data of intestinal content in murine model. Multiple categories associated with normal and high fat diet, NAFLD, NASH and HCC are included.
Project description:Obesity and related metabolic disorders are often characterized by chronic adipose tissue inflammation, driving systemic insulin resistance and general metabolic dysfunction. Free Fatty Acid Receptor 2 (FFA2) has emerged as a potential modulator of adipocyte function, inflammation, and metabolism. To investigate the role of FFA2 expressed in the adipose tissue, we generated adipose-specific FFA2 knockout mice (Adipoq-F2-KO) and assessed metabolic outcomes under standard chow and high-fat, high-sugar Western diet conditions, with and without dietary fiber supplementation. We found that adipose-specific FFA2 deletion had minimal metabolic consequences under standard dietary conditions but significantly reduced body weight and adiposity when mice were fed a fiber (fructooligosaccharide)-supplemented Western diet. Subsequent fecal analyses and transcriptomic profiling indicated impaired intestinal lipid absorption as the primary driver of reduced adiposity, suggesting disrupted adipose-intestinal communication. Unexpectedly, the lighter Adipoq-F2-KO mice also exhibited heightened adipose inflammation, characterized by increased macrophage infiltration and pro-inflammatory cytokine expression. Furthermore, in vitro loss-of-function experiments in adipocytes revealed that FFA2 knockdown impaired adipocyte maturation, lipid storage, and anti-inflammatory signaling. Additional studies using intestinal epithelial cells exposed to adipocyte-conditioned media implicated adipose-derived signals in driving intestinal dysfunction. Collectively, our findings highlight adipose-specific FFA2 as critical in regulating adipose tissue inflammation, lipid metabolism, and inter-organ communication. The data uploaded here specifically contains the comparison of mRNA from mature white adipocytes of FFA2 fl/fl mice compared to RNA from Adipoq-F2-KO mice when both are on a normal chow diet.
Project description:In our study, we investigated the effect of Vasoactive intestinal peptide (VIP) on murine intestinal stem cell (ISC) activity and differentiation in homeostatic conditions and following irradiation-induced injury. We utilized a model of murine intestinal organoids and observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulates epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ ISC under homeostatic conditions. Further analysis revealed that in vitro acute irradiation injury renders Lgr5-EGFP+ ISC even more susceptible to modulations by VIP, which results in the strong promotion of epithelial regeneration by VIP. Finally, these effects by VIP translate into an in vivo model of abdominal irradiation, where VIP was shown to prominently mitigate radiation-induced injury. Taken together, our findings indicate a prominent role of VIP in modulating ISC behavior in intestinal homeostasis and its potential to promote intestinal regeneration following acute irradiation injury.
Project description:Obesity and related metabolic disorders are often characterized by chronic adipose tissue inflammation, driving systemic insulin resistance and general metabolic dysfunction. Free Fatty Acid Receptor 2 (FFA2) has emerged as a potential modulator of adipocyte function, inflammation, and metabolism. To investigate the role of FFA2 expressed in the adipose tissue, we generated adipose-specific FFA2 knockout mice (Adipoq-F2-KO) and assessed metabolic outcomes under standard chow and high-fat, high-sugar Western diet conditions, with and without dietary fiber supplementation. We found that adipose-specific FFA2 deletion had minimal metabolic consequences under standard dietary conditions but significantly reduced body weight and adiposity when mice were fed a fiber (fructooligosaccharide)-supplemented Western diet. Subsequent fecal analyses and transcriptomic profiling indicated impaired intestinal lipid absorption as the primary driver of reduced adiposity, suggesting disrupted adipose-intestinal communication. Unexpectedly, the lighter Adipoq-F2-KO mice also exhibited heightened adipose inflammation, characterized by increased macrophage infiltration and pro-inflammatory cytokine expression. Furthermore, in vitro loss-of-function experiments in adipocytes revealed that FFA2 knockdown impaired adipocyte maturation, lipid storage, and anti-inflammatory signaling. Additional studies using intestinal epithelial cells exposed to adipocyte-conditioned media implicated adipose-derived signals in driving intestinal dysfunction. Collectively, our findings highlight adipose-specific FFA2 as critical in regulating adipose tissue inflammation, lipid metabolism, and inter-organ communication. The data uploaded here specifically contains the comparison of mRNA from mature white adipocytes of FFA2 fl/fl mice compared to RNA from Adipoq-F2-KO mice when both are on a normal chow diet.
Project description:Organoids have the potential to bridge 3D cell culture to tissue physiology by providing a model resembling in vivo organs. We propose here a SILAC method to measure protein expression changes in intestinal organoids under different experimental conditions. With the combined use of quantitative mass spectrometry, SILAC and organoid culture, we validated the approach and showed that large-scale proteome variations can be measured in an “organ-like” system under variable conditions.
Project description:This study uses whole-genome bisulfite sequencing to characterize the methylomes of the AOM/DSS mouse model at single-base resolution. In this model, mice are treated with dextran sodium sulfate (DSS) to induce colitis. When this treatment is preceded by injections of the weak carcinogen azoxymethane (AOM) the mice develop intestinal tumors. Our results identify hypermethylated DMVs as a prominent feature of the colitis methylome that is conserved in intestinal adenocarcinomas. Further analyses reveal a subset of DMV-associated genes, expressed in normal intestinal epithelial cells, that were silenced and hypermethylated in inflamed and cancerous intestinal cells. Together, these findings provide strong support for the hypothesis that inflammatory signals induce a higher risk for cancer development by manipulating the epigenome. . Whole genome methylation analysis of M. musculus. Three conditions were sequenced analyzed, the first is an untreated control, the second corresponds to inflammation, the third to cancer induced by inflammation. All three conditions were analyzed using three replicates.
Project description:Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast Candida albicans colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by C. albicans and exhibited higher fungal load in feces compared to rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. albicans to colonize the high-oleic acid diet-fed mice. RNA-Seq was employed to identify oleic acid-induced transcriptome changes under anaerobic conditions. We identified SOK1 as an oleic acid-induced kinase that dictates cell wall mannan exposure and binding to intestinal mucin under anaerobic conditions. Furthermore, oleic acid induced the expression of several C. albicans transcription factors that positively regulate intestinal colonization via remodeling of the fungal cell surface.