Similar Datasets
Project description:To study sex differences in the response to NASH in mice, single nucleus RNA sequencing of livers was performed. Single nucleus RNAseq demonstrated enrichment of differentially-expressed genes particularly in hepatocytes and stellate cells in females versus males fed FPC-NASH. Multiple regulons (transcription factors and target genes) implicated in lipid and other metabolic processes and hormone signaling (hepatocytes) and cell-cell communication and cell adhesion (stellate cells) were noted, which were enriched in female versus male FPC-NASH diet. Bulk liver RNAseq and RNAseq of isolated hepatocytes and hepatic stellate cells were analyzed as validation experiments.
2024-09-24 | GSE256503 | GEO
Project description:To study sex differences in the response to NASH in mice, single nucleus RNA sequencing of livers was performed. Single nucleus RNAseq demonstrated enrichment of differentially-expressed genes particularly in hepatocytes and stellate cells in females versus males fed FPC-NASH. Multiple regulons (transcription factors and target genes) implicated in lipid and other metabolic processes and hormone signaling (hepatocytes) and cell-cell communication and cell adhesion (stellate cells) were noted, which were enriched in female versus male FPC-NASH diet. Bulk liver RNAseq and RNAseq of isolated hepatocytes and hepatic stellate cells were analyzed as validation experiments.
2024-09-24 | GSE256502 | GEO
Project description:To study sex differences in the response to NASH in mice, single nucleus RNA sequencing of livers was performed. Single nucleus RNAseq demonstrated enrichment of differentially-expressed genes particularly in hepatocytes and stellate cells in females versus males fed FPC-NASH. Multiple regulons (transcription factors and target genes) implicated in lipid and other metabolic processes and hormone signaling (hepatocytes) and cell-cell communication and cell adhesion (stellate cells) were noted, which were enriched in female versus male FPC-NASH diet. Bulk liver RNAseq and RNAseq of isolated hepatocytes and hepatic stellate cells were analyzed as validation experiments.
2024-09-24 | GSE256501 | GEO
Project description:To study sex differences in the response to NASH in mice, single nucleus RNA sequencing of livers was performed. Single nucleus RNAseq demonstrated enrichment of differentially-expressed genes particularly in hepatocytes and stellate cells in females versus males fed FPC-NASH. Multiple regulons (transcription factors and target genes) implicated in lipid and other metabolic processes and hormone signaling (hepatocytes) and cell-cell communication and cell adhesion (stellate cells) were noted, which were enriched in female versus male FPC-NASH diet. Bulk liver RNAseq, RNAseq of isolated hepatocytes and hepatic stellate cells, and spatial transcriptomics, were analyzed as validation experiments.
2024-09-24 | GSE259410 | GEO
Project description:The hallmark of non-alcoholic fatty liver disease (NAFLD) is excessive fatty accumulation in the hepatocytes, which may be an isolated event (non-alcoholic fatty liver, NAFL) or accompanied by evidence of inflammation and cell injury with or without fibrosis (non-alcoholic steatohepatitis, NASH). NASH, the more aggressive form of NAFLD, may progress to cirrhosis and hepatocellular carcinoma. Since NASH is estimated to overtake hepatitis C virus infection as the leading cause of liver transplantation in the US in the coming decade, and there are no current FDA-approved therapies for this disease, the need to find appropriate therapeutic targets is now more urgent than ever before. Diet and other lifestyle modifications have always been difficult to maintain and this approach alone has not slowed the rising tide of the disease. While the results of traditional therapies such as vitamin E and pioglitazone have been significant for steatosis and inflammation, they have had no effect on fibrosis, which is the strongest indicator of mortality in this condition. However, the understanding of the pathogenesis and progression of NASH has evolved and several promising novel therapies to target and possibly reverse fibrosis are being evaluated, making the future outlook of NASH therapy more optimistic.
| S-EPMC5492893 | biostudies-literature
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress
Project description:Ginsenosides have offered a wide array of beneficial roles in the pharmacological regulation of hepatic metabolic syndromes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), and obesity. Of the numerous ginsenosides, Rg3 has been widely investigated, but there have been few studies of gypenosides (Gyp). Particularly, no study on Gyp LXXV has been reported to date. Here, to firstly explore the pharmacological effects of Gyp LXXV against NASH and the related mechanism, methionine- and choline-deficient (MCD) diet-induced NASH mice and hepatic cells (stellate cells, hepatic macrophages, and hepatocytes) were selected. Gyp LXXV exhibited markedly alleviated MCD diet-induced hepatic injury, inflammation, and fibrosis by down-regulating hepatic fibrosis markers such as α-smooth muscle actin(α-SMA), collagen1, transforming growth factors-β (TGF-β1), tumor necrosis factor-α (TNF-α), MCP-1, interleukin (IL)-1β, nuclear factor κB (NFκB), and GRP78. Remarkably, histopathological studies confirmed that 15 mg/kg of Gyp LXXV administration to MCD diet-induced mice led to effective prevention of liver injury, lipid accumulation, and activation of hepatic macrophages, indicating that Gyp LXXV might be a potential anti-NASH drug.
| S-EPMC7599508 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease that ranges from simple steatosis, to inflammatory form non-alcoholic steatohepatitis (NASH), cirrhosis, and up to hepatocellular carcinoma. While NASH usually takes decades to develop at a rate of one stage per seven years, in the case of post-trasplant NASH (pt-NASH) develops fibrosis much more rapidly, with almost 50% of liver transplant recipients presenting stage 3 fibrosis by 5 years post-transplant. Archived fresh-frozen transplanted liver biopsy samples from four liver biopsy samples with evidence of NASH (2 recurrent and 2 de novo), two with simple steatosis (both de novo), and five with normal histology as controls had their transcriptome sequenced in two batches for deeper coverage.
2022-05-09 | E-MTAB-11688 | biostudies-arrayexpress
Project description:Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL) attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.
| S-EPMC4057677 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH; moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or 'Holy Grail' within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.
| S-EPMC7868704 | biostudies-literature