Expression data from livers of control and IlrunKO mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE156151 | GEO | 2020/09/11
REPOSITORIES: GEO
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Project description:Stearoyl-CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1-/- mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1-/- mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage. Experiment Overall Design: RNA was isolated from livers of 10 individual 6-week-old female mice by using a standard method. Mouse genome U74A arrays were used to monitor the expression level of approximately 10,000 genes and expressed sequence tags (Affymetrix). Genes differentially expressed were identified by comparing expression levels in SCD1-/- and wild-type mice.
2007-08-31 | E-GEOD-2926 | biostudies-arrayexpress
Project description:Genetic variants at the TRIB1 (Tribbles-homolog 1) gene locus are strongly associated with plasma lipid traits and the risk of coronary artery disease in humans. In this study, we analyzed the consequences of Trib1-deficiency (Trib1-/-) on hepatic gene expression in mice on the atherosclerosis-susceptible LDL-receptor deficient (Ldlr-/-) background. Therefore, Trib1-/- mice were crossed onto the Ldlr-/- background to generate double knockout mice (Trib1-/-Ldlr-/-) and fed a semisynthetic, modified AIN76 diet (0.02% cholesterol, 4.3% fat). At 20 weeks of age, Trib1-/-Ldlr-/- mice and Trib1+/+Ldlr-/- control mice were sacrificed and liver tissue was snap frozen in liquid nitrogen and stored at -80°C until further processing. Total RNA was isolated from liver tissue (n=8 mice per genotype) and subjected to microarray gene expression analysis.
2023-03-15 | E-MTAB-12669 | biostudies-arrayexpress
Project description:The goal of this study is to understand the role of adipocyte-specific Trib1 in adiponectin and plasma lipid regulation. Here, we report that adipocyte-specific Trib1 knockout mice (Trib1_ASKO) have increased plasma adiponectin levels and decreased plasma cholesterol and triglycerides. We demonstrate that loss of Trib1 increases adipocyte production and secretion of adiponectin independent of the known TRIB1 function of regulating proteasomal degradation. RNA-seq analysis of adipocytes and livers from Trib1_ASKO mice suggests that alterations in adipocyte function underlie the plasma lipid changes observed in these mice. Secretomics and RNA-seq analysis revealed that Trib1_ASKO mice have increased production of Lpl and decreased production of Angptl4 in adipose tissue, and fluorescent substrate assays confirm an increase in adipose tissue Lpl activity, which likely underlies the observed triglyceride phenotype. In summary, we demonstrate here a novel role for adipocyte Trib1 in regulating plasma adiponectin, total cholesterol, and triglycerides in mice, confirming previous genetic associations observed in humans and providing a novel avenue through which Trib1 regulates plasma lipids and coronary artery disease.
2022-06-30 | GSE168596 | GEO
Project description:Objective: Although relationships between smoking and cardiovascular diseases (CVD), and CVD and lipids are established, direct impact of cigarette smoke (CS) on lipidomes remains elusive. We investigated the effect of 6 month smoke exposure on a well-established mouse model for human atherogenesis, Apoe mouse plasma, liver, and aorta molecular lipid profiles and liver transcriptome. // Methods: Plasma, liver, and aorta samples from Apoe mice exposed to CS or fresh air for 6 months were extracted for lipids using robotic-assisted method and analyzed by mass spectrometry. Gene expression of samples from the same livers was obtained on microarrays. Development of atherosclerosis in aorta was further assessed by plaque size measurement in the aortic arch and lipoprotein measurements in plasma and in the plaque. // Results: CS increased most lipid classes and molecular lipid species in tissues evaluated. In plasma, free cholesterol, ceramides, cerebrosides, and majority of phospholipids were increased in CS-exposed mice. In liver, CS elevated several lipid species including free and esterified cholesterol, triacylglycerols, phospholipids, sphingomyelins, and ceramides. In aorta, more than 2-fold higher cholesteryl ester (CE), lysophosphatidylcholine, and glucosyl/galactosylceramide levels were recorded in mice exposed to CS compared to mice exposed to fresh air. Moreover, CS exposure induced a significant decrease in several plasma CE and phosphatidylcholine species that contained polyunsaturated fatty acids. Genes involved in amino acid and lipid metabolism showed perturbed transcription profiles in liver. // Conclusion: These data reveal molecular details accompanying the increase in plaque size, sign of atherogenesis in Apoe mice, which is accelerated by CS exposure.
2013-10-03 | E-MTAB-1195 | biostudies-arrayexpress
Project description:Elevated plasma cholesterol and Type 2 Diabetes (T2D) are associated with Coronary Artery Disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explored the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic and clinical data, we identified a Glucose and Lipid Determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impacted lipid and glucose levels in inverse directions. Experimental knockdown of one of the GLD network master regulators, Lanosterol Synthase (LSS), in mouse confirmed the inverse relationships to glucose and lipid levels as predicted by our model and provided mechanistic insights.
2020-09-01 | GSE157223 | GEO
Project description:Background---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes. Methods and Results---No significant correlation was found between leukocyte counts and plasma lipid levels in 74 individuals. Profiling and analyzing the leukocyte gene expression of 32 individuals revealed distinctive patterns in response to plasma lipid levels: 1) genes involved in lipid metabolism and in the electron transport chain were positively correlated with triglycerides and low-density lipoprotein cholesterol levels, and negatively correlated with high-density lipoprotein cholesterol levels; 2) genes involved in platelet activation were negatively correlated with high-density lipoprotein cholesterol levels; 3) transcription factors regulating lipidgenesis-related genes were correlated with plasma lipid levels; 4) a number of genes correlated to plasma lipid levels were found located in the regions of known QTLs associated with hyperlipemia. Conclusions--- We discovered interesting patterns of leukocyte gene expression in response to plasma lipid levels. Most importantly, genes involved in lipid metabolism, the electron transportation chain, and platelet activation were found correlated with plasma lipid levels. We suggest that leukocytes respond to changing plasma lipid levels by regulating a network of genes, including genes involved in lipid and fatty acid metabolism, through the activation of key transcription factors, such as sterol regulatory element binding transcription factors and peroxisome proliferative activated receptors. Experiment Overall Design: 1. Profile gene expression in human peripheral blood cells. Experiment Overall Design: 2. Test blood biochemistry and blood cell differential counts Experiment Overall Design: 3. Examine the correlation between blood gene expression and blood lipid levels. Experiment Overall Design: 4. Explore possible pathways with significant genes. Experiment Overall Design: 5. Validate a number of significant genes with RT-PCR
2008-06-12 | E-GEOD-3059 | biostudies-arrayexpress
Project description:Stearoyl-CoA desaturase 1-deficient (SCD1-/-) mice have impaired monounsaturated fatty acid (MUFA) synthesis. When maintained on a very low-fat, high-carbohydrate (VLF-HC) diet, SCD1-/- mice develop severe hypercholesterolemia characterized by an increase in apolipoprotein B-containing lipoproteins and the appearance of lipoprotein-X. Additionally, high-density lipoprotein cholesterol is dramatically reduced in VLF-HC SCD1-/- mice. The concomitant presence of elevated plasma bile acids, bilirubin and aminotransferases in the VLF-HC SCD1-/- mouse are indicative of hepatic dysfunction. Supplementation of the VLF-HC diet with unsaturated fat (canola oil), but not saturated fat (coconut oil), prevents these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing low-density lipoprotein cholesterol, signifying an additional role for dietary polyunsaturated fatty acid deficiency in the development of this phenotype. These results indicate that lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Experiment Overall Design: We used Affymetrix Mouse430v2.0 microarray chips to search for gene expression changes unique to the VLF-HC SCD1-/- group. These chips contain 45,101 probe sets representing over 39,000 transcripts and variants from over 34,000 mouse genes. We studied SCD1+/+ and SCD1-/- mice on chow or the VLF-HC diet, analyzing five individual livers from each subgroup for a total of twenty microarrays.
2007-11-01 | E-GEOD-3889 | biostudies-arrayexpress
Project description:The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for three days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic β-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by three days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavourable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet. Keywords: Hepatic gene expression Two-condition experiment. Biological replicates: 4 male rat livers from rats on a standard diet, 4 male rat livers from rats on a cocoa butter diet, 4 male rat livers from rats on a high-fat (safflower oil) diet. One replicate per array.
2010-05-18 | E-GEOD-13936 | biostudies-arrayexpress
Project description:Lysosomal acid lipase (LAL) is the sole lysosomal enzyme responsible for the degradation of cholesteryl esters and triacylglycerols at acidic pH. Impaired LAL activity leads to LAL deficiency (LAL-D), a severe and fatal disease characterized by ectopic lysosomal lipid accumulation. Reduced LAL activity also contributes to the development and progression of non-alcoholic fatty liver disease (NAFLD). To advance our understanding of LAL-related liver pathologies, we performed comprehensive proteomic profiling of livers from mice with systemic genetic loss of LAL (Lal-/-) and from mice with hepatocyte-specific LAL-D (hepLal-/-). Lal-/- mice exhibited drastic proteome alterations, including dysregulation of multiple proteins related to metabolism, inflammation, liver fibrosis, and cancer. Global loss of LAL activity impaired both acidic and neutral lipase activities and resulted in hepatic lipid accumulation, indicating a complete metabolic shift in Lal-/- livers. Hepatic inflammation and immune cell infiltration were evident, with numerous upregulated inflammation-related gene ontology biological process terms. In contrast, both young and mature hepLal-/- mice displayed only minor changes in the liver proteome, suggesting that loss of LAL solely in hepatocytes does not phenocopy metabolic alterations observed in mice globally lacking LAL. These findings provide valuable insights into the mechanisms underlying liver dysfunction in LAL-D and may help in understanding why decreased LAL activity contributes to NAFLD. Our study highlights the importance of LAL in maintaining liver homeostasis and demonstrates the drastic consequences of its global deficiency on the liver proteome and liver function.
2023-10-24 | PXD042478 | Pride
Project description:Purpose: HIF1a inhibitor PX-478 prevents hypercholesterolemia in ApoE-/- mice fed Western diet for 3 months. The goal of this study was to determine the mechanisms in the liver through which PX-478 regulates cholesterol. Methods: 4-week old ApoE-/- mice were fed a Western diet and injected intraperitoneally, bi-weekly with either PX-478 (40 mg/kg) or Saline for 3 months. The livers of 3 PX-478-treated mice and 4 Saline-treated mice were used for this RNA-seq study. Results: We identified 800+ differentially expressed genes in the PX-478-treated ApoE-/- mice livers relative to the saline-treated control livers. A subset of these genes were found to play important roles in cholesterol regulation and were further validated by qPCR analysis. Conclusions: Our study details potential hepatic cholesterol regulating mechanisms for HIF1a inhibitor PX-478. These results, coupled with our findings on the effect of PX-478 on two different mouse models of atherosclerosis, demonstrate that PX-478 is a potential anti-atherogenic and anti-hypercholesterolemic drug.
2022-02-18 | GSE179952 | GEO