Similar Datasets
Project description:mRNA-seq profiles from gastrocnemius muscle of 24-day-old Nnt-wt and Nnt-mut male mice were compared. Result showed that Oxidative phosphorylation (OXPHOS) was the most significantly regulated KEGG pathway. All regulated OXPHOS genes were downregulated in Nnt-mut group. Three genes for carnitine palmitoyltransferase (CPT) system were all downregulated. CPT1B were not changed in protein level but pACC/ACC was increased in Nnt-mut group.
2025-11-15 | GSE255162 | GEO
Project description:BACKGROUND: Clinical management of heart failure with preserved ejection fraction (HFpEF) is hindered by a lack of disease-modifying therapies capable of altering its distinct pathophysiology. Despite the widespread implementation of a 2-hit model of cardiometabolic HFpEF to inform precision therapy, which utilizes HFD+L-NAME (ad libitum high-fat diet and 0.5% N[ω]-nitro-L-arginine methyl ester), we observe that C57BL6/J mice exhibit less cardiac diastolic dysfunction in response to HFD+L-NAME. METHODS: Genetic strain-specific single-nucleus transcriptomic analysis identified disease-relevant genes that enrich oxidative metabolic pathways within cardiomyocytes. Because C57BL/6J mice are known to harbor a loss-of-function mutation affecting the inner mitochondrial membrane protein Nnt (nicotinamide nucleotide transhydrogenase), we established an isogenic model of Nnt loss-of-function to determine whether intact NNT is necessary for the pathological cardiac manifestations of HFD+L-NAME. Twelve-week-old mice cross-bred to isolate wild-type (Nnt+/+) or loss-of-function (Nnt−/−) Nnt in the C57BL/6N background were challenged with HFD+L-NAME for 9 weeks (N=6–10). RESULTS: Nnt+/+ mice exhibited impaired ventricular diastolic relaxation and pathological remodeling, as assessed via noninvasive echocardiographic quantification of early diastolic pulse-wave velocity (E) to mitral annular velocity (e′) ratio (E/e′) (42.8 versus 21.5, P=1.2×10−10), E/A (early-to-late mitral inflow velocity ratio) (2.3 versus 1.4, P=4.1×10−2), diastolic stiffness (0.09 versus 0.04 mm Hg/μL, P=5.1×10−3), and myocardial fibrosis (P=2.3×10−2). Liquid chromatography and mass spectroscopy exposed a 40.0% reduction in NAD+ (P=8.4×10−3) and a 38.8% reduction in the ratio of reduced-to-oxidized glutathione (GSH: GSSG, P=2.6×10−2) among Nnt+/+ mice after HFD+L-NAME feeding. Using single-nucleus ligand-receptor analysis, we implicate Fgf1 (fibroblast growth factor 1) as a putative NNT-dependent mediator of cardiomyocyte-to-fibroblast signaling in myocardial fibrosis. CONCLUSIONS: Together, these findings underscore the pivotal role of mitochondrial dysfunction in HFpEF pathogenesis, implicating both NNT and Fgf1 as novel therapeutic targets.
2025-08-08 | GSE304446 | GEO
Project description:Clinical management of heart failure with preserved ejection fraction (HFpEF) is hindered by a lack of disease-modifying therapies capable of altering its distinct pathophysiology. Despite the widespread implementation of a “two-hit” model of cardiometabolic HFpEF to inform precision therapy, which utilizes ad libitum high-fat and 0.5% N(ω)-nitro-L-arginine methyl ester (HFD+L-NAME) diet, we observe that C57BL6/J mice exhibit less cardiac diastolic dysfunction in response to HFD+L-NAME. Genetic strain-specific single-nucleus transcriptomic analysis identified disease-relevant genes that enrich oxidative metabolic pathways within cardiomyocytes. Because C57BL/6J mice are known to harbor a loss-of-function mutation affecting the inner mitochondrial membrane protein nicotinamide nucleotide transhydrogenase (Nnt), we used an isogenic model of Nnt loss-of-function to determine whether intact NNT is necessary for the pathological cardiac manifestations of HFD+L-NAME. Twelve-week-old mice cross-bred to isolate wild-type (Nnt+/+) or loss-of-function (Nnt-/-) Nnt in the C57BL/6N background, were challenged with HFD+L-NAME for 9 weeks (n = 6-10). Nnt+/+ mice exhibited impaired ventricular diastolic relaxation and pathological remodeling, as assessed via E/e’ (42.8 vs. 21.5, P = 1.2e-10), E/A (2.3 vs 1.4, P = 4.1e-2), diastolic stiffness (0.09 vs 0.04 mmHg/μL, P = 5.1e-3), and myocardial fibrosis (P = 2.3e-2). Liquid chromatography and mass spectroscopy exposed a 40.0% reduction in NAD+ (P = 8.4e-3) and a 38.8% reduction in GSH:GSSG (P = 2.6e-2) among Nnt+/+ mice after HFD+L-NAME feeding. Using single-nucleus ligand-receptor analysis, we implicate fibroblast growth factor 1 (Fgf1) as a putative NNT-dependent mediator of cardiomyocyte-to-fibroblast signaling of myocardial fibrosis. Together, these findings underscore the pivotal role of mitochondrial dysfunction in HFpEF pathogenesis and position both NNT and Fgf1 as novel therapeutic targets.
2025-04-12 | GSE225557 | GEO
Project description:To identify molecular mechanism underlying the protection from diet-induced hepatic steatosis in AHNAK deficiency mice, we examined microarray analysis with liver sample from HFD-fed AHNAK KO and WT mice. Two-condition experiment, regular chow (CD) -fed WT vs. CD-fed AHNAK KO and High fat diet(HFD)-fed WT vs. HFD-fed AHNAK KO mice. Biological replicates: 3 control, One replicate per array.
2015-06-23 | E-GEOD-70119 | biostudies-arrayexpress
Project description:ApoA-IV produced by enterocytes as a major component of high-density lipoprotein plays a role in the satiation signal and also the transport of serum lipids. The present study aimed to investigate the effects of ApoA-IV on diet-induced obesity (DIO), metabolic inflammation and the underlying mechanisms. C57BL/6J ApoA-IV-/- (KO) and wildtype (WT) mice as well as KO mice stably transfected with ApoA-IV-green fluorescent protein (KO-A4-GFP) or solely GFP (KO-GFP) encoding adenoviruses were fed with standard 5% fat rodent chow (CD) or 60% high fat rodent chow (HFD) for 16 weeks.
2022-10-25 | GSE211980 | GEO
Project description:We propose comparing liver gene expression of WT and female ERKO mice early in the high-fat feeding period to animals fed a regular chow diet. Analyzing liver tissue before the fatty liver disease phenotype becomes severe will allow identification of target genes which may be causal. Comparison of regular chow fed WT animals to high fat fed WT animals will allow for identification of hepatic genes up-regulated in response to high fat feeding. Comparison of regular chow fed WT animals to regular chow fed ERKO animals will help clarify hepatic gene expression patterns that may be implicated in increased susceptibility to weight gain and glucose intolerance. Comparison of high fat fed WT animals to high fat fed ERKO animals will provide insight into genes that could be implicated in leading to increased fat accumulation in the liver over time during high fat feeding. Finally, comparison of regular chow fed ERKO animals to high fat fed ERKO animals will help identify genes that may be contributing to increased liver fat accumulation in response to high fat feeding in these animals.
2017-03-22 | GSE95283 | GEO
Project description:High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis. Keywords: gene expression analysis, strain comparision, effect of dietary fat, sex-specific effects One group of mice was fed an atherogenic high-fat (30% fat) diet containing cholic acid to increase fat uptake and another was fed a low-fat (6% fat) regular chow diet. Males and females from both diets were studied for mouse strains 129S1/SvImJ, A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, I/LnJ, MRL/MpJ-Tnfrsf6lpr/J, NZB/BINJ, PERA/Ei, and SM/J. All strains were sacrificed between 11- and 13 weeks of age except for CAST and PERA, which were harvested after 50 weeks of age. CAST and PERA were subsequently removed from our analysis based on discrepant harvest age, but can be found in our database (see below). Three replicate animals were used for each combination of diet, strain, and sex, resulting in a total of 120 mice surveyed for gene expression.
2008-12-10 | E-GEOD-10493 | biostudies-arrayexpress
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of programmed insulin resistant rats offspring from high fat-fed dams vs control offspring from chow fed dams.
2015-04-25 | GSE68225 | GEO
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of programmed insulin resistant rats offspring from high fat-fed dams vs control offspring from chow fed dams. Skeletal muscle (soleus) was collected from the hind limb of 1 year old male offspring (6 from control dams, 6 from high fat-fed dams) . Ramaciotti Centre for Genomics (UNSW, sydney, Australia)
2015-04-25 | E-GEOD-68225 | biostudies-arrayexpress
Project description:High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis. Keywords: gene expression analysis, strain comparision, effect of dietary fat, sex-specific effects
2008-12-10 | GSE10493 | GEO