Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA241275 | ENA |
REPOSITORIES: ENA
Similar Datasets
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. Keywords: repeat (genotype and diet)
2005-12-23 | GSE3889 | 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. Keywords: Atherosclerosis, leukocyte, lipid, gene expression
2006-08-04 | GSE3059 | GEO
Project description:Pomegranate exhibits pronounced hypolipidemic properties, and the objective of this study was to delineate the precise mechanism by which pomegranate facilitates the treatment of hyperlipidemia.SD rats were fed with a high fat diet (HFD) to establish an hyperlipidemia model and intervened with pomegranate .Pomegranate significantly lowered body weight gain , liver weight and adipose tissue coefficient, and attenuated the hepatic steatosis.Serum concentrations of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were markedly reduced, concomitant with a significant elevation in high-density lipoprotein cholesterol (HDL-C) levels. Metabolomic analysis revealed that pomegranate treatment significantly modulated 37 metabolites linked to hyperlipidemia, with the primary pathways affected encompassing sphingolipid metabolism, pyrimidine metabolism, and arachidonic acid metabolism. Transcriptomic profiling identified 439 genes differentially expressed following pomegranate treatment, which were associated with various lipid-related and inflammatory pathways, predominantly including the lipid and atherosclerosis signaling pathway, NF-κB signaling pathway, and TNF signaling pathway.
2024-12-05 | GSE283115 | GEO
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:Autophagy plays vital housekeeping neuronal functions but is not believed to fuel energy metabolism. Autophagy regulation by lipids nutrient sensors have not been identified. Cone photoreceptors’ very-low-density lipoprotein receptor (Vldlr) expression facilitates the uptake of triglyceride-derived fatty acid. In Vldlr-/- mice, we identify free fatty acid receptor 1 (Ffar1) as a suppressor of transcription factor EB (Tfeb), a master regulator of autophagy. Tfeb, in turn, governs the expression of PGC1 and Sirtuin-3, leading to reduced -ketoglutarate (-KG). We recently showed that low -KG in Vldlr-/- photoreceptors drives Vegfa expression and neovascularization reminiscent of a subset of age-related macular degeneration (AMD). Metabolomics of human AMD vitreous and Vldlr-/- retinas identified a similar Krebs cycle metabolite signature. Improving autophagy in AMD-like mice rescued the neovascular phenotype and vision. Dysregulated autophagy may therefore compound the energy failure of photoreceptors contributing to neovascular AMD and could be a driving force in other neovascular diseases.
2022-02-24 | GSE110623 | GEO
Project description:Morgan2016 - Dynamics of cholesterol
metabolism and ageing
This model is described in the article:
Mathematically modelling the
dynamics of cholesterol metabolism and ageing.
Morgan AE, Mooney KM, Wilkinson SJ,
Pickles NA, Mc Auley MT.
BioSystems 2016 Jul; 145: 19-32
Abstract:
Cardiovascular disease (CVD) is the leading cause of
morbidity and mortality in the UK. This condition becomes
increasingly prevalent during ageing; 34.1% and 29.8% of males
and females respectively, over 75 years of age have an
underlying cardiovascular problem. The dysregulation of
cholesterol metabolism is inextricably correlated with
cardiovascular health and for this reason low density
lipoprotein cholesterol (LDL-C) and high density lipoprotein
cholesterol (HDL-C) are routinely used as biomarkers of CVD
risk. The aim of this work was to use mathematical modelling to
explore how cholesterol metabolism is affected by the ageing
process. To do this we updated a previously published
whole-body mathematical model of cholesterol metabolism to
include an additional 96 mechanisms that are fundamental to
this biological system. Additional mechanisms were added to
cholesterol absorption, cholesterol synthesis, reverse
cholesterol transport (RCT), bile acid synthesis, and their
enterohepatic circulation. The sensitivity of the model was
explored by the use of both local and global parameter scans.
In addition, acute cholesterol feeding was used to explore the
effectiveness of the regulatory mechanisms which are
responsible for maintaining whole-body cholesterol balance. It
was found that our model behaves as a hypo-responder to
cholesterol feeding, while both the hepatic and intestinal
pools of cholesterol increased significantly. The model was
also used to explore the effects of ageing in tandem with three
different cholesterol ester transfer protein (CETP) genotypes.
Ageing in the presence of an atheroprotective CETP genotype,
conferring low CETP activity, resulted in a 0.6% increase in
LDL-C. In comparison, ageing with a genotype reflective of high
CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the
model has illustrated the importance of CETP genotypes such as
I405V, and their potential role in healthy ageing.
This model is hosted on
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and identified by:
MODEL1508170000.
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To the extent possible under law, all copyright and related or
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2017-06-01 | MODEL1508170000 | BioModels
Project description:The neuroendocrine regulation of seasonal energy homeostasis and rheostasis are widely studied. However, the molecular pathways underlying tissue-specific adaptations remain poorly described. We conducted an experiment to examine long-term rheostatic changes in energy stability using the well-characterized photoperiodic response of the Japanese quail. We exposed quails to photoperiodic transitions simulating the annual photic cycle and examined the morphology and fat deposition in liver, and white adipose tissue. To identify molecular substrates during the vernal transition in lipid accumulation, we conducted transcriptomic analyses of white adipose and liver tissues. We identified transcripts involved in adipocyte growth (Cysteine Rich Angiogenic Inducer 61, Very Low Density Lipoprotein Receptor) and obesity-linked disease resistance (Insulin-Like Growth Factor Binding Protein 2, Apolipoprotein D) increase expression in anticipation of body mass gain. In the liver, under long photoperiods, transcripts involved in fatty acid (FA) synthesis (Fatty Acid Synthase, Fatty Acid Desaturase 2) were down-regulated. Parallel upregulation of hepatic Fatty Acid Translocase and Pyruvate Dehydrogenase Kinase 4 expression suggests increased circulatory FA uptake and a switch from glucose to FA utilization. Overall, we have identified tissue-specific biochemical and molecular changes that drive photoperiod-induced adipogenesis in quails. These findings can be use to determine conserved pathways that enable animals to accumulate fat without developing metabolic diseases.
2024-07-01 | GSE270939 | GEO
Project description:Objective – Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no FDA-approved anti-calcific therapies. We hypothesized and validated that an unbiased screening approach would identify novel mediators of human vascular calcification. Approach and Results – We performed an unbiased quantitative proteomics and pathway network analysis that identified increased carnitine O-octanoyltransferase (CROT) in calcifying primary human coronary artery smooth muscle cells (SMCs). Additionally, human carotid artery atherosclerotic plaques contained increased immunoreactive CROT near calcified regions. CROT siRNA reduced fibrocalcific response in calcifying SMCs. In agreement, histidine 327 to alanine point mutation inactivated human CROT fatty acid metabolism enzymatic activity and suppressed SMC calcification. CROT siRNA restored mitochondrial proteome alterations and suppressed mitochondrial fragmentation in calcifying SMCs. Lipidomics analysis of SMCs incubated with CROT siRNA revealed increased eicosapentaenoic acid, a vascular calcification inhibitor. CRISPR/Cas9-mediated Crot deficiency in low-density lipoprotein receptor-deficient mice reduced aortic and carotid artery calcification without altering bone density, or liver and plasma cholesterol and triglyceride concentrations. Conclusions – CROT is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an anti-fibrocalcific therapy.
2021-02-26 | PXD022575 | Pride
Project description:Some polyphenols are known to improve the symptoms of diabetes. In the present study, we investigated the effects of a polyphenol-rich extract of maple syrup (MSx) on a diabetic mouse model. KK-Ay mice were fed a normal or 0.05% MSx-supplemented diet for 42 days. Body weight, food intake, serum biochemical parameters, and fecal total bile acid were measured. Gene expression of liver and epididymal white adipose tissue (WAT) and cecal microbiota were analyzed. Data were analyzed with an unpaired two-tailed Student’s t test or Welch’s t test according to the results of the F test. Serum low-density lipoprotein cholesterol levels were significantly reduced in mice that consumed MSx. Hepatic genes related to fatty acid degradation and cholesterol catabolism were upregulated in mice that consumed MSx. In contrast, the expression of genes related to lipid metabolism in WAT was unaffected by the intake of MSx. There were no significant differences between the two groups in terms of total bile acid level in the feces and the relative abundance of bacteria in the cecum. Our results primarily indicate that MSx can help alleviate one of the symptoms of dyslipidemia.
2019-12-17 | GSE112687 | GEO