Metabolomics Workbench ST000686 - GNPS - Lipodomics and Gestational bisphenol A (BPA) exposure
Ontology highlight
ABSTRACT:
INSTRUMENT(S): QTOF - NEGATIVE, QTOF - POSITIVE
ORGANISM(S): Ovis Aries
SUBMITTER: 
Maureen Kachman
PROVIDER: MSV000082726 | GNPS | Thu Aug 02 17:22:00 BST 2018
REPOSITORIES: GNPS
Similar Datasets
Project description:Gestational BPA exposure in sheep induces metabolic phenotype in sheep characterized by peripheral insulin resistance and increased adipocyte size. Because insulin sensitivity can be regulated by various agents including free fatty acids (FFA), we hypothesize that gestational BPA exposure alters circulating FFA inducing dyslipidemia, a marker of metabolic disorder. Because saturated FFA is associated with insulin resistance, determination of the FFA profile in these species aid in understanding the underlying mechanism. Additionally, because of the non-monotonic nature of responses to BPA exposure dose response studies are also needed. This study will therefore assess plasma lipid profile in sheep exposed to three different doses of BPA prenatally and compared with untreated control animals
2016-07-05 | ST000686 | MetabolomicsWorkbench
Project description:Inappropriate developmental exposure to steroids is linked to metabolic disorders. Prenatal testosterone excess or bisphenol A (BPA, an environmental estrogen mimic) leads to insulin resistance and adipocyte disruptions in female sheep. Adipocytes are key regulators of insulin sensitivity and tissue-specific differences in insulin sensitivity, coupled with adipose depot-specific changes in key mRNAs, were previously observed. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) regulators of gene expression would prevail to account for the direction of changes seen in mRNAs. Noncoding RNA (lncRNA, miRNA, snoRNA, snRNA) from various adipose depots of prenatal testosterone and BPA-treated animals were sequenced. Adipose depot-specific changes in the ncRNA that are consistent with the depot-specific mRNA expression in terms of directionality of changes and functional implications in insulin resistance, adipocyte differentiation and cardiac hypertrophy were found. Importantly, the adipose depot-specific ncRNA changes were model-specific that were mutually exclusive suggestive of different regulatory entry points in this regulation.
2024-04-21 | GSE219111 | GEO
Project description:Type 2 Diabetes, obesity and metabolic syndrome are pathologies impacting a large population worldwide where insulin resistance plays a central role. These pathologies are usually associated to a dysregulation of insulin secretion leading to a chronic exposure of the tissues to high insulin levels (i.e. hyperinsulinemia) what diminishes the concentration of key downstream elements causing insulin resistance. The complexity of the study of insulin resistance relies on the heterogeneity of the metabolic states where itM-bM-^@M-^Ys observed. In consequence, animal models for the study of insulin resistance, can not completely recapitulate the metabolic status of insulin resistant humans, what is translated in contradictory observations. To contribute to the understanding of the mechanisms triggering insulin resistance we have developed a zebrafish model to study insulin metabolism and its associated disorders. Zebrafish embryos appeared to be sensitive to human recombinant insulin, becoming insulin resistant when exposed to a high dose of the hormone, as confirmed by glucose measurements. Moreover RNAseq-based transcriptomic profiling of these embryos revealed a strong down regulation of a number of immune relevant genes as a consequences of the exposure to hyperinsulinemia. Interestingly, as an exception, the negative immune modulator ptpn6 appeared to be up regulated in insulin resistant embryos. Knockdown of ptpn6 showed to counteract the observed down regulation of the immune system and insulin signalling pathways effects at the transcriptional level caused by hyperinsulinemia. These results show that ptpn6 is a mediator of the metabolic switch between insulin sensitive and insulin resistant states. Our zebrafish model for hyperinsulinemia has therefore demonstrated it suitability to discover novel regulators of insulin resistance. In addition, our data will be very useful to further study the function of immunological determinants in a non-obese model system. 16 samples in total were analyzed. 4 replicates from control samples (injected with PBS) and 4 replicates of insulin injected samples at 0.5 hpi and 4 hpi. In each sample 10 embryos were pooled.
2014-06-12 | E-GEOD-55836 | biostudies-arrayexpress
Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery.
There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.
| 2744698 | ecrin-mdr-crc
Project description:Type 2 Diabetes, obesity and metabolic syndrome are pathologies impacting a large population worldwide where insulin resistance plays a central role. These pathologies are usually associated to a dysregulation of insulin secretion leading to a chronic exposure of the tissues to high insulin levels (i.e. hyperinsulinemia) what diminishes the concentration of key downstream elements causing insulin resistance. The complexity of the study of insulin resistance relies on the heterogeneity of the metabolic states where it’s observed. In consequence, animal models for the study of insulin resistance, can not completely recapitulate the metabolic status of insulin resistant humans, what is translated in contradictory observations. To contribute to the understanding of the mechanisms triggering insulin resistance we have developed a zebrafish model to study insulin metabolism and its associated disorders. Zebrafish embryos appeared to be sensitive to human recombinant insulin, becoming insulin resistant when exposed to a high dose of the hormone, as confirmed by glucose measurements. Moreover RNAseq-based transcriptomic profiling of these embryos revealed a strong down regulation of a number of immune relevant genes as a consequences of the exposure to hyperinsulinemia. Interestingly, as an exception, the negative immune modulator ptpn6 appeared to be up regulated in insulin resistant embryos. Knockdown of ptpn6 showed to counteract the observed down regulation of the immune system and insulin signalling pathways effects at the transcriptional level caused by hyperinsulinemia. These results show that ptpn6 is a mediator of the metabolic switch between insulin sensitive and insulin resistant states. Our zebrafish model for hyperinsulinemia has therefore demonstrated it suitability to discover novel regulators of insulin resistance. In addition, our data will be very useful to further study the function of immunological determinants in a non-obese model system.
2014-06-12 | GSE55836 | GEO
Project description:Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells.
| PRJNA166857 | ENA
Project description:The goals and objectives: To study Type 2 diabetes progression and the development of insulin resistance in two animal models with and without a high fat diet superimposed on these models. Background: Diabetes is a systemic metabolic imbalance involving multiple tissues/organs, and an early hallmark feature of this disease state is insulin resistance. Multifactorial interactions of genetics, prenatal environmental factors (fetal programming) and postnatal environmental factors (nutrition and activity) likely contribute to the diabetic phenotype.Animal models can serve as a valuable tool for studying diabetes disease progression and for identifying useful biomarkers of type 2 diabetes. Several inbred rodent models are available for diabetes related studies. The GK rat is an obvious choice among available inbred models as the genetic basis for this inheritable form of diabetes is polygenic (5), unlike most other inbred rodent models that exhibit single gene defects. Many of the characteristics of the GK rat mirror human diabetes (hyperglycemia, glucose intolerance, insulin resistance), although hyperlipidemia does not appear to be prominent in the GK rat. Due to its polygenic mode of inheritance and 100% penetrance, the GK rat may be a useful model for human diabetes. Induced animal models can also be useful in diabetes studies. One such model is metabolic syndrome resulting from experimentally induced fetal programming (produced by maternal malnutrition or by exposure to corticosteroids in the third trimester). Both in humans and animals, accumulating evidence suggests that alterations in the human fetal environment can result in permanent physiologic changes that manifest as increased incidence of adult onset pathology. Numerous epidemiological studies have forged a strong link between low birth weight and the development of metabolic syndrome in adulthood. From such observations has arisen the concept of âfetal programmingâ whereby exposure to some factor(s) during crucial stages in development can permanently alter or âresetâ physiologic/metabolic functions. In the rat, exposure to corticosteroids during a âwindowâ in third trimester gestation (CS programming) results in fetal growth retardation and insulin resistance in adult offspring. Genetic factors play a primarily role in the etiology of diabetes in the GK rat, whereas fetal environmental factors are causative in CS programming. (It should be noted that although altered fetal environmental effects, most likely stemming from maternal hyperglycemia, have been implicated to play some role in the decreased pancreatic B cell mass in GK rats, these effects occur earlier in gestation and therefore differ from programming by CS in late gestation.) A comparison of the development of insulin resistance in the GK rat with development in the CS programmed rat will provide insight into genetic and fetal environmental factors in disease development. Superimposing dietary alterations (i.e., high fat feeding) (11) on both animal models may aid in the dissection of multiple interacting factors (genetic, fetal environmental factors, postnatal environmental factors) on the development and progression of insulin resistance and type 2 diabetes. Such studies may also aid in the identification of useful biomarkers for insulin resistance and type 2 diabetes in humans. Proposed research: Experiments are designed to study disease progression and the development of insulin resistance in two animal models: the GK rat and the CS programmed rat, with and without a high fat diet superimposed on these models. Animals will be maintained in our facility from weaning (GK rats) or birth (CS programmed - WKY), and body weights taken weekly. Appropriate diets (normal or high fat) will be introduced at weaning. Groups of animals (N=6) will be sacrificed at 5 different ages: 4, 8, 12, 16, and 20 weeks. Plasma samples will be analyzed for markers of hyperglycemia, hyperinsulinemia, dyslipidimia, and for selected other hormonal factors which may contribute to disease etiology (adiponectin, leptin, corticosterone). At sacrifice, muscle is harvested, flash-frozen in liquid nitrogen, and warehoused in our tissue collection maintained at - 80 degrees C for this and possible future work. Study will initially focus on examination of selected molecular markers of insulin resistance at the mRNA level in rat abdominal fat (PEPCK, IRS-1). Experiment Overall Design: The study contains: 50 adipose tissue samples from GK (GotoKakizake) rats and 51 adipose tissue samples from WKY (WistarKyoto) rats feeded with normal diet (ND) and high fat diet (HFD) and sacrificed at 5 different ages: 4, 8, 12, 16, and 20 weeks. So, each time point contains 5 GK samples with ND, 5 GK samples with HFD, 5 WKY samples with ND and 5 WKY samples with HFD.
2009-11-10 | E-GEOD-13268 | biostudies-arrayexpress
Project description:The goals and objectives: To study Type 2 diabetes progression and the development of insulin resistance in two animal models with and without a high fat diet superimposed on these models. Background: Diabetes is a systemic metabolic imbalance involving multiple tissues/organs, and an early hallmark feature of this disease state is insulin resistance. Multifactorial interactions of genetics, prenatal environmental factors (fetal programming) and postnatal environmental factors (nutrition and activity) likely contribute to the diabetic phenotype.Animal models can serve as a valuable tool for studying diabetes disease progression and for identifying useful biomarkers of type 2 diabetes. Several inbred rodent models are available for diabetes related studies. The GK rat is an obvious choice among available inbred models as the genetic basis for this inheritable form of diabetes is polygenic (5), unlike most other inbred rodent models that exhibit single gene defects. Many of the characteristics of the GK rat mirror human diabetes (hyperglycemia, glucose intolerance, insulin resistance), although hyperlipidemia does not appear to be prominent in the GK rat. Due to its polygenic mode of inheritance and 100% penetrance, the GK rat may be a useful model for human diabetes. Induced animal models can also be useful in diabetes studies. One such model is metabolic syndrome resulting from experimentally induced fetal programming (produced by maternal malnutrition or by exposure to corticosteroids in the third trimester). Both in humans and animals, accumulating evidence suggests that alterations in the human fetal environment can result in permanent physiologic changes that manifest as increased incidence of adult onset pathology. Numerous epidemiological studies have forged a strong link between low birth weight and the development of metabolic syndrome in adulthood. From such observations has arisen the concept of âfetal programmingâ whereby exposure to some factor(s) during crucial stages in development can permanently alter or âresetâ physiologic/metabolic functions. In the rat, exposure to corticosteroids during a âwindowâ in third trimester gestation (CS programming) results in fetal growth retardation and insulin resistance in adult offspring. Genetic factors play a primarily role in the etiology of diabetes in the GK rat, whereas fetal environmental factors are causative in CS programming. (It should be noted that although altered fetal environmental effects, most likely stemming from maternal hyperglycemia, have been implicated to play some role in the decreased pancreatic B cell mass in GK rats, these effects occur earlier in gestation and therefore differ from programming by CS in late gestation.) A comparison of the development of insulin resistance in the GK rat with development in the CS programmed rat will provide insight into genetic and fetal environmental factors in disease development. Superimposing dietary alterations (i.e., high fat feeding) (11) on both animal models may aid in the dissection of multiple interacting factors (genetic, fetal environmental factors, postnatal environmental factors) on the development and progression of insulin resistance and type 2 diabetes. Such studies may also aid in the identification of useful biomarkers for insulin resistance and type 2 diabetes in humans. Proposed research: Experiments are designed to study disease progression and the development of insulin resistance in two animal models: the GK rat and the CS programmed rat, with and without a high fat diet superimposed on these models. Animals will be maintained in our facility from weaning (GK rats) or birth (CS programmed - WKY), and body weights taken weekly. Appropriate diets (normal or high fat) will be introduced at weaning. Groups of animals (N=6) will be sacrificed at 5 different ages: 4, 8, 12, 16, and 20 weeks. Plasma samples will be analyzed for markers of hyperglycemia, hyperinsulinemia, dyslipidimia, and for selected other hormonal factors which may contribute to disease etiology (adiponectin, leptin, corticosterone). At sacrifice, muscle is harvested, flash-frozen in liquid nitrogen, and warehoused in our tissue collection maintained at - 80 degrees C for this and possible future work. Study will initially focus on examination of selected molecular markers of insulin resistance at the mRNA level in rat liver (PEPCK, PDK4). Experiment Overall Design: The study contains: 50 liver samples from GK (GotoKakizake) rats and 51 liver sample from WKY (WistarKyoto) rats feeded with normal diet (ND) and high fat diet (HFD) and sacrificed at 5 different ages: 4, 8, 12, 16, and 20 weeks. So, each time point contains 5 GK samples with ND, 5 GK samples with HFD, 5 WKY samples with ND and 5 WKY samples with HFD.
2009-11-10 | E-GEOD-13270 | biostudies-arrayexpress
Project description:We report the RNA-sequencing analysis of hepatic RNA isolated from CD-1 mice following gestational exposure to 500ppb CdCl2. We show that gestational Cd exposure alters the hepatic gene expression of female, but not male offspring in numerous pathways related to oxidative stress and mitochondrial dysfunction leading to endoplasmic reticulum stress that ultimately drives metabolic disruption of insulin signaling.
2020-12-09 | GSE150679 | GEO