Effect of perinatal obesity on premature kidney aging signaling
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000
ORGANISM(S): Mus musculus
SUBMITTER: Katrin Bohl
PROVIDER: E-MTAB-10954 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:During the last few decades, the long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident, but the effects of maternal nutrition on the developing intestine are currently still relatively underexplored. In this study, we investigated in mice the effects of a maternal Western-style (WS) high fat/cholesterol diet, given during the perinatal period, on gene expression and microbiota composition of two-week-old offspring. Microarray analysis revealed that a perinatal WS diet caused significant changes in gene expression in the small intestine and colon of the suckling offspring. A strong sexually dimorphic effect was observed in the affected genes. However, pathway analysis of the differentially expressed genes displayed that in both sexes metabolic and immune functions were strongly affected. Integration of the microbiota and gene expression data applying a multivariate correlation analyses revealed that Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae were the bacterial families that most strongly correlated with gene expression in the colon and not with the bacterial families displaying the most pronounced change due to perinatal exposure to a WS diet. Amongst the genes demonstrating a strong correlation with one or more bacterial families were genes of key importance for intestinal development or functioning (i.e., Pitx2 and Ace2). In conclusion, our data demonstrate a strong programming effect of a maternal WS diet on the development of the intestine in the offspring. Small intestine and colon were isolated from two-week-old pups of dams fed a low- or Western-style high fat/cholesterol diet and subjected to gene expression profiling.
2016-08-22 | E-GEOD-72705 | biostudies-arrayexpress
Project description:Background. Resistant Starch (RS) improves CKD outcomes. In this report we study how RS modulates host-microbiome interactions in CKD by measuring changes in abundance of proteins and bacteria in the gut. In addition, we demonstrate RS-mediated reduction in CKD-induced kidney damage. Methods. Eight mice underwent 5/6 nephrectomy to induce CKD and 8 served as healthy controls. CKD and Healthy (H) groups were further split into those receiving RS (CKDRS, n=4; HRS, n=4) and those on normal diet (CKD, n=4, H, n=4). Kidney injury was evaluated by measuring BUN/creatinine and by most-mortem histopathological evaluation. Cecal contents were analyzed mass spectrometry-based metaproteomics. PEAKS Studio was used to identify peptides via de novo sequencing. A set of R/Bioconductor packages and in house written scripts was further used to infer bacteria present, to evaluate changes in proteins and bacterial abundances, and to perform statistical analysis and hierarchical clustering. Results. The 5/6 nephrectomy compromised kidney function as seen by an increase in creatinine and BUN. Representative photomicrographs of trichrome-stained kidney sections showed reduced tubulointerstitial injury in CKD mice fed HAM-RS2 diet comparing to CKD mice fed normal diet. Identified organisms and proteins point toward a higher population of butyrate-producing bacteria, and reduced abundance of mucin-degrading bacteria. Conclusion. Resistant starch slows the progression of chronic kidney disease. Gut barrier function through maintenance of the mucin barrier plays a role in RS-associated improvements in CKD phenotype. Resistant starch supplementation leads to the active bacterial proliferation and the reduction of harmful bacterial metabolites.
2020-10-19 | PXD019623 | Pride
Project description:The etiopathogenesis of obesity-related chronic kidney disease (CKD) is still scarcely understood. Aim of this study is to shed light on the molecular pathogenesis of obesity-induced CKD by assessing the effect of high fat diet (HF) on molecular pathways leading to organ damage, steatosis, and fibrosis. Six-week-old male C57BL/6N mice were fed HF diet or normal chow for 20-weeks. Kidneys were collected for genomic, proteomic, histological studies and lipid quantification. The main findings were as follows: 1) HF diet activated specific pathways leading to fibrosis and increased fatty acid metabolism; 2) HF diet promoted a metabolic shift of lipid metabolism from peroxisomes to mitochondria; 3) no signs of lipid accumulation and/or fibrosis were observed, histologically; 4) the early signs of kidney damage seemed to be related to changes in membrane protein expression and/or oxidative stress; 5) the proto-oncogene MYC was the top upstream transcriptional regulator of changes occurring in protein expression. These results demonstrated the potential usefulness of specific selected molecules as early marker of injury in HF, while histomorphological changes become visible late in CDK progression. The integration of these data with data from biological fluids could help the identification of biomarkers useful for the clinical practice.
2022-05-20 | PXD031915 | Pride
Project description:Maternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.
2013-08-13 | E-GEOD-49797 | biostudies-arrayexpress
Project description:Objective Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment. Examination of differentially expressed genes between gestational day 15 (+/- 0.5 days) C57BL/6 mouse fetal livers from diet-induced (60% fat diet) obese or control female mice.
2014-10-25 | E-GEOD-62715 | biostudies-arrayexpress
Project description:Objective: Procyanidins are polyphenolic bioactive compounds that exert beneficial effects against obesity and its related diseases. The aim of this study was to evaluate whether the supplementation with low doses of a grape seed procyanidin extract (GSPE) to dams during pre and postnatal periods has biological effects on their offspring at youth. Design: The metabolic imprinting effect of GSPE was evaluated in 30 days-old male offspring of four groups of rats that were fed either a standard diet (STD) or a high-fat diet (HFD) and supplemented with either GSPE at 25 mg per kg of body weight/day or vehicle during pregnancy and lactation. Results: A significant increase in the adiposity index and in the weight of all the white adipose tissue depots studied (retroperitoneal â??RWAT-, mesenteric â??MWAT-, epididymal â??EWAT- and inguinal â??IWAT-) was observed in offspring of dams fed with a HFD and treated with GSPE (HFT group), compared to the offspring of dams fed with the same diet and that do not received procyanidins (HF group). HFT animals also showed a higher number of cells in the EWAT, a sharply decrease of the circulating levels of monocyte chemoattractant protein-1 (MCP-1) as well as a moderate, but significant, decrease of plasma glycerol levels. The transcriptomic analysis performed in the EWAT showed 238 genes differentially expressed between HF and HFT animals, covering an entire range of processes related with the immune function and the inflammatory response (the metabolic pathway mainly reflected in the EWAT), adipose tissue remodeling and function, lipid and glucose homeostasis and metabolism of methyl groups. Conclusion: GSPE treatment to dams fed a HFD during pregnancy and lactation increases adiposity, decreases the circulating levels of MCP-1 and modulates the expression of key genes involved in the adipose tissue metabolism of their offspring. The microarray study was performed with the EWAT RNA samples of rats from the HF and the HFT groups (n=8 animals each).
2016-03-26 | E-GEOD-57005 | biostudies-arrayexpress
Project description:Prenatal iron deficiency (pID) has been described to increase the risk for neurodevelopmental disorders such as autism and schizophrenia; however, the precise molecular mechanisms are still unknown. Here, we utilized high throughput mass spectrometry to examine the proteomic effects of pID in adulthood on the rat frontal cortex area (FCA). In addition, the FCA proteome was examined in adulthood following risperidone treatment in adolescence to see if these effects could be prevented. We identified 1501 proteins of which 100 were significantly differentially expressed in the FCA at post-natal day 90. Pathway Analysis of proteins affected by pID revealed changes in metabolic processes, including the tricyclic acid cycle, mitochondrial dysfunction, and P13K/Akt signaling. Interestingly, most of these protein changes were not present in the adult pID offspring who received risperidone in adolescence. Behavioral testing of pID rats demonstrated social impairment and poor performance during novelty-induced exploration in pID animals in line with a abnormal neurodevelopmental phenotype. Considering the link between prenatal iron deficiency and several neurodevelopmental disorders such as autism and schizophrenia these presented results bring new perspectives to understand the role of iron in metabolic pathways and provide novel biomarkers for future studies of prenatal iron deficiency.
2018-07-05 | PXD004975 | Pride
Project description:Chronic kidney disease (CKD) is a burden for Public Health and concerns millions of individuals worldwide. Independently of the cause, CKD is secondary to the replacement of functional renal tissue by extra-cellular matrix proteins (i.e fibrosis) that progressively impairs kidney function. The pathophysiological pathways that control the development of renal fibrosis are common to most of the nephropathies involving native kidneys or kidney grafts. Unfortunately, very few treatments are available to stop renal fibrosis and most of the therapeutic strategies are often barely able to slow down the progression of fibrogenesis in native kidneys. Therefore, it is mandatory to discover new therapeutic pathways to stop renal fibrosis. Our objective is to study new pathways involved in renal fibrosis. We thus decided to use the model of Unilateral Ureteral renal Obstruction in mice, a fast and reproducible experimental model of renal fibrosis. We studied renal fibrosis using experimental model of ureteral unilateral obstruction in mice, which was performed by complete ligation of the left ureter. The control lateral right kidney served as internal control.
2013-02-10 | E-GEOD-38117 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) is the gradual, asymptomatic loss of kidney function and current tests only identify it when significant loss has already happened. Using RNA sequencing in a mouse model of folic acid (FA) induced nephropathy, here we report the identification of 10 genes that track kidney fibrosis development, the common pathological finding in CKD patients. The gene expression of all 10 candidates was confirmed to be significantly high (~ 10-150 fold) in three well-established and mechanistically distinct mouse models of kidney fibrosis. Protein expression was also high in the FA model as well as patients with biopsy-proven kidney fibrosis. The specificity of these 10 candidates for kidney fibrosis was demonstrated by showing a very modest (~ 2-5 fold) increase in the mouse models of acute kidney injury as well as following liver fibrosis in mice and humans. Using targeted selected reaction monitoring mass spectrometry (SRM-MS) we found that 3 out of 10, cadherin 11 (CDH11), mannose receptor C1 (MRC1), phospholipid transfer protein (PLTP), are detectable in human urine. Furthermore, the levels of CDH11 and MRC1 are able to distinguish patients with chronic kidney disease from healthy individuals (n = 78, p<0.01). In summary, we report the identification of CDH11 and MRC1 as novel non-invasive biomarkers of CKD. mRNA sequencing of mouse kidney before and at various time points (1,2,3,7 & 14 days) after intraperitoneal treatment with folic acid.
2015-10-23 | E-GEOD-65267 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) is a very important problem in global health treatment. CKD increases the disease risk of apoplexy, cardiac failure and cardiac infarction. In addition, neurological complications, including depression and restless legs syndrome, occur in almost all CKD patients; however, the mechanisms of these neurological complications remain unclear. Here, we showed the disruptive effect of chronic renal failure in 5/6 nephrectomy mice on an immobility time of forced swim and tail suspension test and the 24-hr rhythm of Drd2 and clock gene expressions in the striatum. These disruptive effects were induced by abnormal signal transduction in high TGF-M-NM-21 expression from the kidney. Abnormal TGF-M-NM-2 signal in the striatum led to TCF7L2 expression and ID2 induced by TCF7L2 led to disruption of the 24-hr rhythm of clock gene expression. These findings suggest that neurological complications in CKD might be overcome by amelioration of the TGF-M-NM-2 signal. Differential gene expression between 5/6 nephrectomized and sham-operated mouse was measured on the brain.
2013-08-01 | E-GEOD-35134 | biostudies-arrayexpress