Apolipoprotein A-I Influences The Transcriptional Profile Of Fatty Liver In Apolipoprotein E Knockout Mice
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ABSTRACT:
PROVIDER: PRJNA1146900 | ENA |
REPOSITORIES: ENA
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Project description:Fatty liver disease is a condition characterized by lipid accumulation in the hepatocytes and it is generally accompanied by a dyslipidemic condition characterized by low HDL levels. Being the interrelation between fatty liver disease and low HDL not clearly understood, in the present study, the impact of different apoA-I/HDL levels on the transcriptome of diet-induced fatty liver was investigated. Eight-week-old mice lacking apoA-I/HDL (DKO) and mice with physiological levels of apoA-I/HDL (DKO/hA-I) were fed either a standard rodent diet (SRD) or a Western diet (WD) for 22 weeks. Steatosis was quantified, and the hepatic transcriptome was analyzed by RNAseq. Following WD, both genotypes showed marked lipid accumulation in the liver, without relevant histological differences. The transcriptome analysis showed an upregulated expression of immune/inflammatory genes and a reduced activation of the retinoid metabolism in both WD-fed genotypes. Strong divergences in genes involved in metabolic pathways were observed only in the presence of apoA-I/HDL, where the results suggested reduced endogenous biosynthesis of cholesterol and other sterols, glutathione metabolism together with increased glucose metabolism. In conclusion, although not histologically overt, apoA-I/HDL seems to exert a substantial impact on hepatic metabolism during steatosis, that goes beyond cholesterol metabolism.
2025-07-18 | GSE274510 | GEO
Project description:Objective: Recent genome-wide association studies (GWAS) identified a variant rs7575840 in the apolipoprotein B (APOB) gene region to be associated with LDL-C. However, the underlying functional mechanism of this variant that resides 6.5 kb upstream of APOB has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB containing lipid particles; for replication in a non-Caucasian Mexican population; and for underlying functional mechanism. Methods and Results Our data show that rs7575840 is associated with serum apoB levels (P=4.85x10-10) and apoB containing lipid particles, very small VLDL, IDL and LDL particles (P=2x10-5 - 9x10-7) in the Finnish METSIM study sample (n=7,710). Fine mapping of the APOB region using 43 SNPs replicated the association of rs7575840 with apoB in a Mexican study sample (n=2,666, P=3.33x10-05). Furthermore, our transcript analyses of adipose RNA samples from 175 Finnish METSIM subjects indicate that rs7575840 alters expression of APOB (P=1.13x10-10) and a regional non-coding RNA (BU630349) (P=7.86x10-6) in adipose tissue. Conclusions It has been difficult to convert GWAS associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB containing lipid particles as well as influences expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant SNP rs7575840 may affect serum apoB, LDL-C, and TC levels. 175 samples, no replicates
2011-08-31 | E-GEOD-27666 | biostudies-arrayexpress
Project description:Objective: Recent genome-wide association studies (GWAS) identified a variant rs7575840 in the apolipoprotein B (APOB) gene region to be associated with LDL-C. However, the underlying functional mechanism of this variant that resides 6.5 kb upstream of APOB has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB containing lipid particles; for replication in a non-Caucasian Mexican population; and for underlying functional mechanism. Methods and Results Our data show that rs7575840 is associated with serum apoB levels (P=4.85x10-10) and apoB containing lipid particles, very small VLDL, IDL and LDL particles (P=2x10-5 - 9x10-7) in the Finnish METSIM study sample (n=7,710). Fine mapping of the APOB region using 43 SNPs replicated the association of rs7575840 with apoB in a Mexican study sample (n=2,666, P=3.33x10-05). Furthermore, our transcript analyses of adipose RNA samples from 175 Finnish METSIM subjects indicate that rs7575840 alters expression of APOB (P=1.13x10-10) and a regional non-coding RNA (BU630349) (P=7.86x10-6) in adipose tissue. Conclusions It has been difficult to convert GWAS associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB containing lipid particles as well as influences expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant SNP rs7575840 may affect serum apoB, LDL-C, and TC levels.
2011-09-01 | GSE27666 | GEO
Project description:Increased amounts of the mitochondrial apolipoprotein O /MIC26 were found in diabetic patients along with lipid accumulation in murine liver upon MIC26 expression. MIC26 is a MICOS complex constituent present in the mitochondrial inner membrane. Here, we employed a proteomics analysis approach in WT and MIC26 knockout HepG2 cellular models in normoglycemic and hyperglycemic conditions.
2024-09-13 | PXD047246 | Pride
Project description:The conserved WhiA protein family is present in most Gram-positive bacteria and plays a role in cell division. WhiA contains a DNA-binding motive and has been identified as a transcription factor in the actinomycetes. In Bacillus subtilis, a deletion of whiA influences cell division and chromosome segregation. However, WhiA does not seem to function as a transcription factor in this organism, and it is still unclear how WhiA influences these processes. The B. subtilis whiA gene is part of an operon and flanked by two metabolic genes, including yvcK required for growth under gluconeogenic conditions, and the gene encoding the catabolite repressor Crh. Therefore, B. subtilis WhiA might play a role in carbon metabolism which could indirectly affect cell division and chromosome maintenance. To study this, we followed a metabolomics approach and measured exo-metabolome flux during growth on different carbon sources, using nuclear magnetic resonance spectroscopy. The carbon utilization of wild type and whiA mutant cells was similar, however, the whiA mutant exhibited depleted pools of branched-chain fatty acid precursors and higher levels of acetate and 2-oxoglutarate. Transcriptome data could not link these effects to gene regulatory differences, but the reduction in branched-chain fatty acid precursors influenced the fatty acid composition of the cell membrane. In conclusion, WhiA does not participate in carbon catabolite regulation, but affects fatty acid composition of the membrane by an as yet unknown mechanism. We speculate that the effect on the membrane might be related to the pleiotropic phenotype of the B. subtilis whiA mutant.
2019-10-18 | GSE121479 | GEO
Project description:Nitric oxide (NO) is a crucial gaseous signaling molecule engaged in a variety of physiological and pathological processes. It is produced by three isoenzymes called nitric oxide synthases (NOS): neuronal, inducible and endothelial NOS (eNOS). eNOS-derived NO plays an important role in endothelium-dependent vasodilation as well as in lipid and glucose homeostasis in the liver. In addition, it has been shown that NO exert a beneficial effect on mitochondrial biogenesis and respiration. Thus, the aim of our study was to used iTRAQ-based quantitative proteomics to investigate the changes in protein expression in the mitochondrial and cytosolic fractions isolated from the liver of the double (apolipoprotein E (apoE) and eNOS) knockout (apoE/eNOS-DKO) mice as compared to apoE-/- mice – an animal model of atherosclerosis and hepatic steatosis. Collectively, our proteomic approach revealed the increased expression of proteins related to gluconeogenesis, fatty acids and cholesterol biosynthesis as well as the decreased expression of proteins participated in triglyceride breakdown, cholesterol transport, protein transcription & translation and processing in endoplasmic reticulum (ER). Moreover, one of the most down-regulated proteins were major urinary proteins (MUPs), which are abundantly expressed in the liver and are involved in the regulation of lipid and glucose metabolism as well as mitochondrial function. However, the exact functional consequences of the revealed alterations require further investigation.
2018-03-05 | PXD006642 | Pride
Project description:Interventions: experimental group :PD-1 Knockout Engineered T Cells
Primary outcome(s): Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Study Design: historical control
| 2662961 | ecrin-mdr-crc
Project description:Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype.
| S-EPMC5524844 | biostudies-literature
Project description:Eight weeks old double apolipoprotein E and apolipoprotein A-I knockout mice (DKO) were fed either normal laboratory diet (chow) or high-fat (Western) diet for 6 or 22 weeks. High-throughput sequencing technologies were used to analyse the transcriptome of the aorta of apolipoprotein E knockout (EKO, GSE163657) and DKO mice to showcase the use of the software reString (https://github.com/Stemanz/restring), a functional enrichment results aggregator.
2021-11-22 | GSE173974 | GEO