Letter: gender-associated cell-free microRNA profiles in non-alcoholic fatty liver disease.
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ABSTRACT:
SUBMITTER: Longchamps RJ
PROVIDER: S-EPMC4007279 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
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Letter: gender-associated cell-free microRNA profiles in non-alcoholic fatty liver disease.
Longchamps R J RJ Abey S K SK Martino A C AC Henderson W A WA
Alimentary pharmacology & therapeutics 20140501 9
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Project description:Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.
| S-EPMC9267237 | biostudies-literature
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
Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans. Animal models DD Shionogi (DS), Fatty Liver Shionogi (FLS Wild; W), and FLS ob/ob mice were subjected as the normal control, SS model and NASH model, respectively. Male DS mice (Riken BRC No. 03706) were provided by Riken bio-resource center through the national bio-resource project of Japan. Male FLS W and male FLS-ob/ob mice were obtained from Shionogi research laboratories (Shiga, Japan). Animals were housed in a room maintained at a controlled temperature of 24 ± 2 Ë?C under a 12-h light-dark cycle. Animals were provided ad libitum access to water and standard pellet feed. Five male mice of every strain (24 weeks old; mean body weight of DS, FLS W and FLS-ob/ob were 31.1 ± 1.1g, 38.4 ± 3.4g and 56.0 ± 5.0g, respectively) were sacrificed under pentobarbital anesthesia by whole blood collection from the right ventricle. The livers were cut into about 200 mg pieces and fixed in 10% formalin for histological analysis or fresh-frozen in liquid nitrogen and stored at -80 °C in a freezer until use. miRNA expression analysis Total RNAs in mouse liver were isolated using TrizolReagent (Life Technologies, California, USA) as described the manufacturerâ??s protocol. The quality of total RNA samples was checked by applying the RNA Integrity Number (RIN) which is calculated by a proprietary algorithm of the Agilent 2100 Bioanalyzer expert software (Agilent technologies, CA, USA). Only high quality RNA, with RNA integrity number (RIN) greater than 8 and A260/280 and A260/230 greater than 1.8, will be considered for microarray analysis. TaqMan® Array Rodent MicroRNA A Card v2.0 (Thermo Fisher Scientific, MA, USA) was used to assess 375 miRNA expression profiles in mouse liver tissue.
2016-07-03 | E-GEOD-69670 | biostudies-arrayexpress
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.
2013-08-30 | GSE49542 | GEO
Project description:The diagnosis of fibrosis within liver disease is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. The rising incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) has driven the search for accurate non-invasive tools of liver fibrosis within this condition. With the aid of a systematic review, we explore how the field has evolved from the discovery of simple blood parameters to panel markers of liver fibrosis. We will discuss the biological plausibility, limitations, potential uses, and emerging diagnostic techniques of non-invasive markers in this rapidly expanding field.
| S-EPMC1860097 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of about 25%. Incidence is increasing with rising levels of obesity, type 2 diabetes and the metabolic syndrome, and NAFLD is predicted to become the leading cause of cirrhosis requiring liver transplantation in the next decade. However, the cardiovascular disease is the most common cause of death and only a minority will develop fibrosis and liver-related complications. Therefore, it is imperative to identify patients with advanced disease using non-invasive markers of fibrosis, which include serology-based tests (eg NAFLD Fibrosis Score and ELF test) and imaging (eg transient elastography). This targets appropriate patients for referral to secondary care for additional investigations such as liver biopsy and specialist care. Lifestyle modification and weight loss remains the cornerstone of management, but we are about to enter a new era of promising pharmacotherapies for NASH and fibrosis.
| S-EPMC6334080 | biostudies-literature
Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans.
2016-01-01 | GSE69670 | GEO
Project description:Background & aimsLittle is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography.MethodsWe performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ≥30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included.ResultsApproximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78).ConclusionsIndividuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.
| S-EPMC6758911 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-β, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes.
| S-EPMC9225218 | biostudies-literature
Project description:Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.
| S-EPMC4959750 | biostudies-literature