Cardiac hypertrophy is associated with growth and functional changes of cardiomyocytes,including mitochondrial alterations, but the latter are still poorly understood. Here we investigated mitochondrial function and dynamic localization in neonatal rat ventricular cardiomyocytes (NRVCs) stimulated with insulin like growth factor 1 (IGF1) or phenylephrine (PE), mimicking physiological and pathological hypertrophic responses,respectively.
Hypertrophy induced KIF5B controls mitochondrial localization and function in neonatal rat cardiomyocytes.
Specimen part
View SamplesAnalysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother
Sex-dependent programming of glucose and fatty acid metabolism in mouse offspring by maternal protein restriction.
Sex, Specimen part
View SamplesRight ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load.
Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.
Sex, Specimen part
View SamplesMedium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD-/- mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD-/- mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1a (Pgc-1a) and decreased peroxisome proliferator-activated receptor alpha (Ppar a) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD-/- mice in both conditions,suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD-/- mice. During the APR, however, this flux was significantly decreased (-20%) in MCAD-/- mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD-/- mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD-/- mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD-/- mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation.
Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice.
Sex, Specimen part, Treatment
View SamplesPerinatal nutritional imbalances may have long-lasting consequences on health and disease, increasing risk of obesity, insulin resistance, type 2 diabetes or cardiovascular disease. This idea has been conceptualized in the Developmental Origins of Health and Disease Hypothesis (DOHaD). In addition, there is evidence that such early-programmed phenotypes can be transmitted to the following generation(s). It is proposed that, environmentally induced, transmission of disease risk is mediated by epigenetic mechanisms.
In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered Lxra DNA methylation.
Specimen part, Treatment
View SamplesThe ACBP knockout were created by targeted disruption of the gene in mice. The expression profiling was performed on liver tissue from ACBP-/- (KO) and +/+ (WT) mice at the age of 21 days, which in our study is the time immediately before weaning. The mice used for this experiment were taken directly away from their mother. Thus, having free access to chow and breast milk until sacrificed at 8-11am
Disruption of the acyl-CoA-binding protein gene delays hepatic adaptation to metabolic changes at weaning.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Specimen part, Disease, Disease stage, Subject
View SamplesTo acquire a better understanding of the molecular pathogenesis of HS, we performed mRNA microarray studies to compare gene expression in lesional skin to healthy skin of HS patients.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Subject
View SamplesTo acquire a better understanding of the molecular pathogenesis of hidradenitis suppurativa (HS), we performed mRNA microarray studies to compare whole blood gene expression of HS patients to that of healthy normal subjects.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Specimen part, Disease, Disease stage, Subject
View SamplesBackground: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants.
Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome.
Specimen part
View Samples