ABSTRACT: Metabolic modeling of gut microbiota in high-fat diet induced nonalcoholic steatohepatitis through barrier dysfunction and shaping of intrahepatic immunity are ameliorated by VSL#3 supplementation
Project description:The genomic landscape of hepatic tissue affected by nonalcoholic steatohepatitis (NASH) in severely obese adolescents undergoing bariatric surgery is unknown. Our purpose here was to uncover genomic profiles of obese controls, and obese cases with nonalcoholic fatty liver disease (NAFLD), borderline nonalcoholic steatohepatitis, and definite nonalcoholic steatohepatitis, in order to clarify molecular functions, biological processes, and pathways that are dysregulated in nonalcoholic steatohepatitis in the severely obese adolescent. In a prospective observational cohort study, we have intra-operatively obtained 165 liver samples; of these 67 were submited for microarray analysis. Through ANOVA, we found 8648 genes with differential regulation between the four histologies; from these, we uncovered gene signatures shared between borderline and definite nonalcoholic steatohepatitis, and gene sets with differential effects between borderline and definite.
Project description:BCAA were administered to atherogenic and high-fat (Ath & HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice and platelet-derived growth factor C transgenic mice (Pdgf-c Tg). Liver histology, tumor incidence, and gene expression profiles were evaluated. BCAA supplementation improved hepatic steatosis, inflammation, fibrosis, and tumors in the NASH mouse model, possibly through the modification of mTORC1 signaling.
Project description:Intrahepatic macrophages in nonalcoholic steatohepatitis (NASH) are heterogenous and include proinflammatory recruited monocyte derived macrophages. RAGE is expressed on macrophages and can be activated by damage associated molecular patterns (DAMPs) upregulated in NASH, yet the role of macrophage-specific RAGE signaling in NASH is unclear. Therefore, we hypothesized that a subset of RAGE expressing macrophages are proinflammatory and mediate liver inflammation in NASH. We profiled the transcriptome of intrahepatic leukocytes in a murine model of diet induced NASH in WT and RAGE-MKO mice. By Nanostring nCounter Immunology Codeset Analysis of IHLs, we observed that myeloid-specific RAGE deletion resulted in amelioration of activation of macrophage and T cell pathways which was associated with attenuation of liver inflammation.
Project description:We examined the potential utility of L-carnitine for alleviating metabolic dysfunction-associated steatohepatitis (MASH) and preventing the development of hepatocellular carcinoma. Short-term L-carnitine administration ameliorated MASH through its anti-inflammatory effects.
Project description:Intrahepatic macrophages in nonalcoholic steatohepatitis (NASH) are heterogenous and include proinflammatory recruited monocyte derived macrophages. RAGE is expressed on macrophages and can be activated by damage associated molecular patterns (DAMPs) upregulated in NASH, yet the role of macrophage-specific RAGE signaling in NASH is unclear. Therefore, we hypothesized that a subset of RAGE expressing macrophages are proinflammatory and mediate liver inflammation in NASH. We profiled the transcriptome of intrahepatic leukocytes in a murine model of diet induced NASH where mice received vehicle or a pharmacological RAGE inhibitor (TTP488). By Nanostring nCounter Immunology Codeset Analysis of IHLs, we observed that RAGE inhibition resulted in amelioration of FFC diet induced activation of macrophage and T cell pathways which was associated with attenuation of liver inflammation.
Project description:Liver is an important organ for fat metabolism. Excessive intake of a high-fat/energy diet is a major cause of hepatic steatosis and its complications such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Supplementation with lycopene, a natural compound, is effective in lowering triglyceride levels in the liver, although the underlying mechanism at the translational level is unclear. In this study, mice were fed a high-fat diet (HFD) to induce hepatic steatosis and treated with or without lycopene. Translation omics and transcriptome sequencing were performed on the liver to explore the regulatory mechanism of lycopene in liver steatosis induced by HFD, and identify differentially expressed genes (DEGs).
Project description:Purpose: We investigated the tetrachloroethylene associated changes in kidney transcriptomes among healthy mice, nonalcoholic fatty liver disease mice, and nonalcoholic steatohepatitis mice.
