Project description:Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MALFD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear. Methods: Liver tissue from 21 participants was collected at time of bariatric surgery and analyzed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n=3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. Mouse models of hepatic steatosis were used to investigate observations made from human liver tissue. Results: We observed variable degrees of liver steatosis with minimal fibrosis in our participants. Single-cell RNA sequencing revealed four macrophage clusters that exist in the human fatty liver encompassing Kupffer cells (KC) and monocyte-derived macrophages (MdM). The genes expressed in these macrophage subsets were similar to those observed in mouse models of MAFLD. Hepatic CD14+ monocytes/macrophage number correlated with the degree of steatosis. Using mouse models of early liver steatosis we demonstrate recruitment of MdMs precedes KC loss and liver damage and that MdMs may serve a role in lipid uptake during MAFLD. Conclusions: The human liver in MAFLD contains macrophage subsets that align well with those that appear in mouse models of fatty liver disease. Recruited myeloid cells correlate well with the degree of liver steatosis in humans and this occurs prior to changes in KC number. MdMs appear to have a role in lipid uptake during early stages of MALFD.
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes but their molecular pathogenesis is not fully elucidated. Global RNA sequencing of snap frozen liver tissue from 98 patients with biopsy-proven NAFLD was performed. Unsupervised hierarchical clustering well-distinguished NASH from NAFL, and NASH patients exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified multiple secreted proteins upregulated in NASH and/or advanced fibrosis
Project description:We identified the differentially expressed miRNAs in Landes goose liver after overfeeding for 21 days using high-throughput sequencing. We obtained 21453493 and 21525819 clean reads in normal liver and fatty liver by high-throughput sequencing, respectively. Of these clean reads, we respectively gained 9244896 and 9847086 miRNAs sequences in two groups by filtering the known non-miRNA reads, such as rRNA, tRNA, snRNA, and snoRNA by screening against ncRNA deposited in the GenBank and Rfam databases. These findings provided insights into the expression profiles of miRNAs in goose liver, and deepened our understanding of miRNAs in hepatic steatosis of geese.
Project description:Alcohol induced fatty liver cause a dangerous health problem and is the major cause of morbidity and mortality worldwide. Garlic (Allium sativum) is documented to possess anti-fatty liver properties. However the exact molecular mechanisms are unknown. The main aim of this experiment is to elucidate the underlying pathways through which garlic ameliorates alcohol induced fatty liver. Dially disulfide and garlic oil were the garlic compounds used in this study. Leiber DeCarli ethanol liquid diet was to induce fatty liver in C57BL/6 mice model. Also the expression impaired by alcohol induced fatty liver is another aim of this study.
Project description:This study aimed to explored the effects and underlying mechanisms of Tormentic Acid (TA) against metabolic-associated fatty liver disease (MAFLD) in mice. The differentially expressed genes (DEGs) in liver tissue in “Normal VS model ”and “Model VS TA” were identified by RNA-seq.
Project description:Alcohol induced fatty liver cause a dangerous health problem and is the major cause of morbidity and mortality worldwide. Garlic (Allium sativum) is documented to possess anti-fatty liver properties. However the exact molecular mechanisms are unknown. The main aim of this experiment is to elucidate the underlying pathways through which garlic ameliorates alcohol induced fatty liver. Dially disulfide and garlic oil were the garlic compounds used in this study. Leiber DeCarli ethanol liquid diet was to induce fatty liver in C57BL/6 mice model. Also the expression impaired by alcohol induced fatty liver is another aim of this study. Leiber-Decarli ethanol diet was used to induce fatty liver in male C57BL/6 mice (n=12). For control, Lieber-DeCarli liquid control diet was fed to mice (n=4). The control mice were pair-fed to the ethanol mice. After adaptation, the ethanol fed mice were divided into three groups viz. alcohol (n=4), dially disulfide [DADS] (n=4) and garlic oil [GO] (n=4). The study started with the administration of DADS (15 mg/kg bw) or GO (50 mg/kg bw) mixed in 0.1 ml olive oil through gavage. For the control and alcohol groups, same amount of olive oil (0.1 ml) was gavaged. The mice were gavaged daily for 4 weeks. The mice were euthanized by CO2 and blood was collected by cardiac puncture. Liver, kidney, spleen, lungs and hearts were collected and their weights recorded. A portion of liver was snap frozen in liquid nitrogen (200 mg) for RNA extraction.