Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of Tesamorelin on Hepatic Transcriptomic Signatures in HIV-Associated NAFLD

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity among people living with HIV with a more aggressive course than in the general population. In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone-releasing hormone analogue tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over one year. In the current study, we leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by tesamorelin versus placebo to gain key insights into the biological underpinnings of its clinical effects.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150026 | GEO | 2020/09/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Microarray analysis of choline-deficient L-amino acid-defined (CDAA) diet-induced NAFLD animal model.

Project description:Nonalcoholic Fatty Liver Disease (NAFLD) is a broad spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. The choline-deficient L-amino acid-defined (CDAA) diet-induced NAFLD animal model has traditionally been used to understand the molecular mechanisms of disease development and progression. Although this animal model shows a similar course of disease progression to human NAFLD, it does not develop comorbidities such as obesity and type 2 diabetes. Therefore, its relevance to human NAFLD (what aspects of the disease etiology are recapitulated in this model?) is not fully understood. We applied microarray analysis to characterize its pathophysiology, and evaluate the similarity across species.

2023-03-25 | GSE227714 | GEO

Dyslipidemia Alters HDL Metabolism and Function in NAFLD

Project description:Dyslipidemia and inflammation play key roles in the pathogenesis of both nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. NAFLD, particularly its severe form nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular disease (CVD) risk. HDL (high density lipoprotein- also a CVD risk) are decreased in NAFLD but whether HDL function is abnormal in NAFLD is unknown. Furthermore, it is unknown whether dyslipidemia contributes to reduced HDL function in NAFLD and whether hepatic inflammation further impairs HDL function in patients with NASH. Therefore, the aim of this study was to investigate HDL function and to examine the effect of dyslipidemia and inflammation on HDL metabolism in patients with biopsy-proven simple steatosis (SS) and NASH. RESULTS: Compared to controls, SS and NASH subjects had significantly higher levels of plasma triglyceride, insulin, and were more insulin resistant (HOMA, P<0.05) with no differences in total cholesterol, HDL cholesterol, ApoB100 and ApoAI levels. NAFLD patients had increased production and degradation rates of both HDLc and ApoAI that resulted in their levels remaining stable. The degradation rates also were increased of other HDL proteins, including ApoAII, ApoAIV, vitamin D-binding protein, and complement 3 (all P<0.05). NAFLD patients had increased activities of LCAT and CETP, indicating altered HDL lipidation. NAFLD induced alterations in HDL metabolism were associated with reduced anti-oxidant but increased pro-inflammatory activity of HDL. However, no differences were observed in either HDL function or the kinetics of HDLc and HDL proteins between SS and NASH subjects.

2019-08-12 | PXD010199 | Pride

miRNA profiling in human nonsteatotic and NAFLD livers

Project description:To investigate the function of miRNAs in liver, we obtained liver tissues from nonsteatotic individuals and fatty livers from patients with nonalcoholic fatty liver disease (NAFLD). Patients due to excessive alcohol consumption, autoimmune liver disease, viral hepatitis and diabetes were excluded. Nonsteatotic livers were collected from the normal region of the livers from donors who received liver resection due to liver hemangioma, and were defined as those with NASH activity scores of 0 We then performed miRNA sequencing using livers from two NAFLD patients and two nonsteatotic individuals.

2023-03-12 | GSE227021 | GEO

TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Human_liver_RNA_seq]

Project description:The goals of this study are to investigate whether the defects of energy metabolism and/or mitochondria occurs in Nonalcoholic fatty liver disease (NAFLD), we performed liver transcriptome analysis from livers of donors who underwent organ donation after cardiac death (DCD; 6 non-NAFLD donors, 5 NAFLD donors). In this screen, a cluster of 462 transcripts were up-regulated and 447 transcripts were down-regulated in response to NAFLD. Among these differentially expressed genes , gene sets that contribute to endoplasmic reticulum stress, intrinsic apoptosis and cytokine production were enriched in NAFLD livers, whereas lipid metabolic process were suppressed in NAFLD livers, accompanied with deficient expression of the mitochondrial matrix enzyme.

2021-02-17 | GSE160016 | GEO

Cullin-associated and neddylation-dissociated protein 1 (CAND1) alleviates NAFLD by reducing ubiquitinated degradation of ACAA2

Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder with high morbidity and mortality. The current study aims to explore the role of Cullin-associated and neddylation-dissociated protein 1 (CAND1) in the development of NAFLD and the underlying mechanisms. CAND1 is reduced in the liver of NAFLD male patients and high fat diet (HFD)-fed male mice. CAND1 alleviates palmitate (PA) induced lipid accumulation in vitro. Hepatocyte-specific knockout of CAND1 exacerbates HFD-induced liver injury in HFD-fed male mice, while hepatocyte-specific knockin of CAND1 ameliorates these pathological changes. Mechanistically, deficiency of CAND1 enhances the assembly of Cullin1, F-box only protein 42 (FBXO42) and acetyl-CoA acyltransferase 2 (ACAA2) complexes, and thus promotes the ubiquitinated degradation of ACAA2. ACAA2 overexpression abolishes the exacerbated effects of CAND1 deficiency on NAFLD. Additionally, androgen receptor binds to the -187 to -2000 promoter region of CAND1. Collectively, CAND1 mitigates NAFLD by inhibiting Cullin1/FBXO42 mediated ACAA2 degradation

2023-10-24 | PXD043719 | Pride

Study of the Association of Nonalcoholic Fatty Liver Disease With Colorectal Malignant Neoplasm

Project description:The aim of this sudy is to investigate the prevalence of colorectal cancer (CRC) in patients with nonalcoholic fatty liver disease (NAFLD) and evaluate whether NAFLD is a risk factor for CRC.

| 2129836 | ecrin-mdr-crc

Hepatic mitochondrial proteome dynamics in NAFLD mice

Project description:Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in LDLR-/- mice. In addition, compared to controls, livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting reduced mitochondrial oxidative capacity. Proteome dynamics analysis revealed that mitochondrial dysfunction is associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41±0.46 vs. 5.15±0.49 day, P<0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome c oxidase subunit 4 isoform 1 of complex III (5.9 ± 0.1 vs 3.4 ± 0.8 day), ATP synthase subunit α (6.3±0.4 vs. 5.5±0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5±0.6 vs. 6.5±0.2 day) (P<0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities, suggesting that increased degradation of mitochondrial proteins contributed to hepatic mitochondrial dysfunction in NAFLD mice. Autophagy, but not proteasomal degradation, contributed to increased clearance of hepatic mitochondrial proteins in NAFLD mice. In conclusion, the proteome dynamics approach suggests that alterations in mitochondrial proteome dynamics is involved in hepatic mitochondrial dysfunction in NAFLD.

2018-11-21 | PXD008766 | Pride

circRNA expression profiles of fibroblasts: normal vs. NASH cirrhosis

Project description:The progression from steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) patients is one of the major causes of liver-related death worldwide and have limited effective therapies. We comparing the circular RNomics of liver fibroblasts isolated from patients with NAFLD-caused cirrhosis and the ones without NAFLD.

2019-07-31 | GSE134146 | GEO

RNA-seq of human with nonalcoholic fatty liver disease against untreated controls

Project description:We analyzed the transcriptome for drug metabolism genes of 35 human (17 healthy control (HC), and 18 nonalcoholic fatty liver disease (NAFLD)) liver tissues, obtained during laparoscopic cholecystectomy. The aim of our study is to identify the drug metabolism genes significantly regulated by NAFLD at the transcriptome level.

2022-12-19 | E-MTAB-12445 | biostudies-arrayexpress

Lack of associations of microRNAs with severe NAFLD in people living with HIV: Discovery case-control study

Project description:The aim of this discovery case-control study was to identify patterns of differential expression of microRNAs in people living with HIV (PLWH) and assess their diagnostic value for non-alcoholic fatty liver disease (NALFD). Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, body mass index, CD4+ lymphocyte count, active HCV infection, and ART regimen. Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study. Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.

2023-05-03 | E-MTAB-12974 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data