Similar Datasets
Project description:Nonalcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) easily progresses toward severe forms of nonalcoholic steatohepatitis (NASH) and fibrosis, and the underlying mechanism is under active investigation. Here, we established the role of transcription factor 7-like 2 (TCF7L2), the most significant T2D susceptibility gene, in NAFLD development and progression. Hepatic TCF7L2 expression was decreased in liver biopsies of patients with NAFLD. Based on the major risk factors for NAFLD development, liver-specific TCF7L2 knockout mice were subjected to a high-fat diet providing fatty acids (FAs) and refeeding/high-carbohydrate diet stimulating de novo lipogenesis. Hepatic TCF7L2 deficiency significantly increased the lipid synthetic pathways and hepatic TG accumulation by preferentially metabolizing carbohydrates than FAs. Mechanistically, TCF7L2 regulated miRNAs targeting SREBF1c and enhanced proteasome-mediated MLXIPL (ChREBP) degradation. Our findings will deepen the pathophysiological mechanism of NAFLD associated with dietary carbohydrate and diabetes, and will provide a potential target for treatment of NAFLD.
2023-01-09 | GSE162449 | GEO
Project description:Low carbohydrate diet study for non-alcoholic fatty liver disease patients
| PRJNA420975 | ENA
Project description:OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. RESULTS Body weight was reduced, insulin sensitivity (HOMA-IR) was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. CONCLUSIONS Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.
2019-02-05 | GSE103682 | GEO
Project description:Our aim was to evaluate the potential of gene expression profiling in blood in a human intervention study investigating the effect of two breakfasts with different macronutrient content on hormonal regulation of satiety. As dietary protein appears to be more satiating than dietary carbohydrate, we tested the differential effect of a high protein and a high carbohydrate breakfast on satiety.
2008-08-07 | E-TABM-271 | biostudies-arrayexpress
Project description:Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. Previously we have shown that TSP1 plays an important role in obesity-associated metabolic complications including inflammation, insulin resistance, cardiovascular and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) remains largely unknown and is determined in this study. High fat diet or AMLN diet-induced obese and insulin resistant NAFLD/NASH mouse models were utilized. In addition, tissue specific TSP1 knockout mice were utilized to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development. The data demonstrated that liver TSP1 levels were increased in experimental obese and insulin resistant NAFLD/NASH mouse models as well as in human obese NASH patients. Moreover, TSP1 deletion in hepatocyte or adipocytes did not protect mice from diet-induced NAFLD/NASH. However, myeloid/macrophage-specific TSP1 deletion protected mice against obesity-associated liver injury, accompanied by reduced liver inflammation and fibrosis. Importantly, this protection is independent of the levels of obesity and hepatic steatosis. Mechanistically, through an autocrine effect, macrophage-derived TSP1 suppressed SMPDL3B expression in liver, which amplified liver pro-inflammatory signaling (TLR4 signal pathway) and promoted NAFLD progression. Together, out data suggest that macrophage-derived TSP1 is a significant contributor to obesity-associated NAFLD/NASH development and progression and may serve as a therapeutic target for this disease.
2020-12-07 | GSE155973 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients with all stages of NAFLD and controls were analysed by array-based DNA methylation and mRNA expression profiling. Bisulphite converted DNA from the 85 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2013-08-08 | E-GEOD-48325 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.
2022-06-16 | GSE184113 | GEO
Project description:With an estimated prevalence of about 30% in western countries non-alcoholic fatty liver disease (NAFLD) is a major public health issue [PMID: 18956290]. NAFLD is associated with the metabolic syndrome of insulin resistance, obesity, glucose intolerance. Although many studies are pointing to an induction of insulin resistance by NAFLD causality between both phenotypes is not fully clarified. Furthermore, mechanisms leading to strongly differing progression of NAFLD have to be elucidated which range from mild steatosis up to severe steatohepatitis. Steatohepatitis might even result in liver cirrhosis and hepatocellular carcinoma. Additional complexity is introduced into the understanding of the disease by recent studies providing evidence for a direct development of carcinoma from steatosis without the formerly assumed intermediary phase of cirrhosis. Here, we investigate liver samples from patients with varying severities of steatosis in an integrative approach employing transcriptomics, serum biomarker profling, metabolomics data and systems biology models. Total RNA obtained from hepatocytes derived from nine obese patients with distinct grades of steatosis. This dataset is part of the TransQST collection.
2015-11-01 | E-GEOD-46300 | biostudies-arrayexpress
Project description:Nonalcoholic fatty liver disease (NAFLD) is a common disorder in obese people and is becoming the leading cause of hepatocellular carcinoma (HCC). Recently, lncRNAs have been proven to play remarkable roles in numerous biological processes and human diseases, including NAFLD. However, the function of lncRNA in NAFLD pathogenesis remains largely unknown. The aim of this study was to explore the lncRNA expression profile in NAFLD mice and to identify novel lncRNAs involved in the pathogenesis of NAFLD. We performed microarray analysis to compare the expression profiles of lncRNAs and mRNAs in the liver of diabetic db/db mice with NAFLD and normal mice.
2017-12-19 | GSE108228 | GEO
Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.
2013-08-30 | E-GEOD-49542 | biostudies-arrayexpress