Functional genomics study on Non Alcoholic fatty liver disease (NAFLD)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Cultured Cells
DISEASE(S): Fatty Liver Disease
PROVIDER: ST000678 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
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Project description: Not available
| ST000680 | MetabolomicsWorkbench
Project description:Irisin is a cytokine involved in many metabolic pathways occurring, among others, in muscles, adipose tissue and liver. Thus, fluctuations in irisin levels are suggested to be related to metabolic diseases. Therefore, the purpose of our study was to evaluate whether irisin may be associated with non-alcoholic fatty liver disease (NAFLD). A total of 138 patients (70/68 male/female, mean age 65.61 ± 10.44 years) were enrolled in the study. The patients were assigned to the NAFLD group (n = 72, including 46 patients with type 2 diabetes (T2DM]) and the group without NAFLD (n = 66, 31 patients with T2DM). NAFLD was diagnosed based on ultrasound examination, Hepatic Steatosis Index (HSI) and Fatty Liver Index. Baseline anthropometric, blood pressure and biochemical parameters were collected. The serum irisin level was determined using an ELISA test. We observed that NAFLD was associated with an increased concentration of irisin. Moreover, Spearman correlations and linear regression analysis revealed that irisin level correlates with some anthropometric and biochemical parameters such as body mass index, glycated hemoglobin, aspartic aminotransferase, creatinine and urea. Logistic regression analysis depicted that odds for NAFLD increase 1.17 times for each 1 μg/mL rise of irisin concentration. Finally, ROC analysis showed that the concentration of irisin possesses a discriminate capacity for NAFLD and optimal cut points concentration could be designed. The risk of NAFLD in the subgroup with irisin concentration above 3.235 μg/mL was 4.57 times higher than in patients with the lower concentration of irisin. To conclude, the obtained results suggest that irisin concentration is associated with some anthropometric and biochemical parameters and should be further investigated toward its usage as a diagnostic biomarker of NAFLD.
| S-EPMC9496390 | biostudies-literature
Project description:6-8-week-old male C57BL/6 were divided into 2 groups after 12 weeks on the HFD diet, and tail vein injections of either an Adenoviral vector (with Adenoviral type 5 backbone) containing Ad-GFP-m-ACOT1 or Ad-GFP at 1x109 PFU were performed weekly for 4 weeks
2021-05-21 | GSE174797 | GEO
Project description:Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A's functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 ?mol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true "vitamin A deficiency", but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.
| S-EPMC5793257 | biostudies-other
Project description:Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the liver and is often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, and other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD in 2020 as metabolic (dysfunction) associated with fatty liver disease (MAFLD). The changes in diet and lifestyle are recognized the non-drug treatment strategies; however, due to the complex pathogenesis of NAFLD, the current drug therapies are mainly focused on its pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. There is still a lack of specific drugs. In clinical studies, the common NAFLD treatments include the regulation of glucose and lipid metabolism to protect the liver and anti-inflammation. The NAFLD treatments based on the enterohepatic axis, targeting gut microbiota, are gradually emerging, and various new metabolism-regulating drugs are also under clinical development. Therefore, this review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.
| S-EPMC9884828 | biostudies-literature
Project description:PurposeThe Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort is a population-based study designed to examine the interaction between genetic and lifestyle factors and their association with increased risk of NAFLD within the Indian population.ParticipantsBetween 2013 and 2016, a total of 2222 participants were recruited to this cohort through multistage cluster sampling across the whole population of Trivandrum-a district within the state of Kerala, South India. Data were collected from all inhabitants of randomly selected households over the age of 25.Findings to dateFull baseline clinical and pathological data were collected from 2158 participants. This included detailed demographic profiles, anthropometric measures and lifestyle data (food frequency, physical activity and anxiety and depression questionnaires). Biochemical profile and ultrasound assessment of the liver were performed and whole blood aliquots were collected for DNA analysis.The NAFLD prevalence within this population was 49.8% which is significantly higher than the global pooled prevalence of 25%. This highlights the importance of robust, prospective studies like this to enable collection of longitudinal data on risk factors, disease progression and to facilitate future interventional studies.Future plansThe complete analysis of data collected from this cohort will give valuable insights into the interaction of the phenotypic and genotypic profiles that result in such a dramatic increased risk of NAFLD within the Indian population. The cohort will also form the basis of future lifestyle interventional studies, aimed at improving liver and metabolic health.
| S-EPMC6502065 | biostudies-literature
Project description: Not available
| S-EPMC1954961 | biostudies-literature
Project description:Inter-individual and inter-ethnic differences and difference in the severity and progression of liver disease among patients with non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) suggests the involvement of genetic and epigenetic factors in their pathogenesis. This article reviews the genetic and epigenetic modifiers in patients with NAFLD and ALD. Evidence regarding the genetic and epigenetic disease modifiers of NAFLD and ALD was reviewed by searching the available literature. Both genome wide association studies (GWAS) and candidate gene studies pertaining to the pathogenesis in both diseases were included. Clinical implications of the available information are also discussed. Several studies have shown association of both NAFLD and ALD with I148M PNPLA3 variant. In addition to the higher prevalence of hepatic steatosis, the I148M PNPLA3 variant is also associated with severity of liver disease and risk of hepatocellular carcinoma (HCC). TM6SF2 is the other genetic variant shown to be significantly associated with hepatic steatosis and cirrhosis in patients with NAFLD and ALD. The Membrane bound O-acyltransferase domain-containing 7 (MBOAT7) genetic variant is also associated with both NAFLD and ALD. In addition to these mutations, several variants related to the genes involved in glucose metabolism, insulin resistance, lipid metabolism, oxidative stress, inflammatory pathways, fibrosis have also been shown to be the disease modifiers in patients with NAFLD and ALD. Epigenetics involving several micro RNAs and DNA methylation could also modify the disease course in NAFLD and ALD. In conclusion the available literature suggests that genetics and epigenetics are involved in the pathogenesis of NAFLD and ALD which may affect the disease prevalence, severity and response to treatment in these patients.
| S-EPMC7724177 | biostudies-literature
Project description:6-8-week-old male C57BL/6 were divided into 2 groups after 12 weeks on the HFD diet, and tail vein injections of an Adenoviral vector containing Ad-GFP-U6-scramble-shRNA or Ad-GFP-U6-m-ACOT1-shRNA at 1x109 PFU were performed weekly for 6 weeks (Vector Biolabs)
2021-05-25 | GSE175426 | GEO
Project description:Background and aimsThe prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally. This study aimed to determine the prevalence of NAFLD and the probability of liver fibrosis in Italian primary care services.MethodsWe carried out a population-based and nested case-control study including all individuals aged 18 years and above registered at Italian primary care services. Data were collected from the general practitioners' network from 2010 to 2017. NAFLD cases were identified via the ICD-9-CM and Hepatic Steatosis Index score > 36 and were matched each up to 10 controls. Other causes of liver diseases were excluded. The risk of fibrosis was assessed using the FIB-4 and NAFLD fibrosis scores (NFS).ResultsNAFLD was present in 9% of the primary care population with high regional variability. Among NAFLD subjects: 25% had diabetes, 10% had chronic kidney disease, 11% had cardiovascular disease and 28% were obese. Furthermore, 30% had at least two comorbidities and 13% had cirrhosis. Once cirrhosis was excluded, the risk of any degree of fibrosis was 13.8% with NFS and 20.5% with FIB-4 in subjects <65 years.ConclusionsEven if there is an identification gap in primary care, recorded cases with NAFLD have a high frequency of associated comorbidities. Despite regional variability, a close relation between cirrhosis and NAFLD exists (OR: 3.48, 95% CI: 3.23-3.76). Therefore, the use of non-invasive tests should be promoted in primary care as a useful tool for the early identification of fibrosis risk, independently of evidence of steatosis.
| S-EPMC9827935 | biostudies-literature