High fat diet and sciatic nerves functions
Ontology highlight
ABSTRACT:
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Blood
DISEASE(S): Neuropathy
SUBMITTER: 
Maureen Kachman
PROVIDER: ST000780 | MetabolomicsWorkbench | Mon Jun 05 00:00:00 BST 2017
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Six strain/genotype combinations (BKS wt, BKS db/+, ?) were fed control (5LOD) or high fat (54 % lard) chow from 5 to 36 weeks of age. Longitudinal changes in small and large nerve fiber function, glucose tolerance, fasting blood glucose, body weight etc. were assessed in all groups
2018-08-02 | MSV000082738 | GNPS
Project description:Plasma, kidney, sciatic nerve, and retina samples collected from control (db/m) and diabetic (db/db) mice. Samples snap frozen and stored at -80. Plasma volume measured and tissues weighed for lipid extraction.
2017-06-05 | ST000672 | MetabolomicsWorkbench
Project description:A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve. Microarray data for 24 week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further used for functional enrichment analysis and network analysis to identify biological processes and pathways differentially regulated in the db/db nerve. Expression profile clustering was performed to identify co-expressed DEGs. A set of co-expressed lipid metabolism genes was used for promoter sequence analysis.We identified 4,017 DEGs; 2,122 genes were up-regulated and 1,895 genes were down-regulated in the db/db relative to the db+ samples. Over-represented biological processes identified by the functional enrichment analysis include cell cycle, lipid metabolic process, lipid transport, carbohydrate metabolic process, response to stress, apoptosis, axonogenesis and cell adhesion. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, PPAR signaling, apoptosis, and axon guidance. The majority of DEGs in the glycolysis, TCA cycle, oxidative phosphorylation, fatty acid metabolism, glycerolipid metabolism, mitochondrial fatty acid elongation, lipid transport, adipocytokine signaling, PPAR signaling, and apoptosis pathways are up-regulated, whereas most of the axonogenesis-related genes are down-regulated in db/db nerve. A network of DEGs based on their co-citation in literature identified regulatory relationship between Tnf-α and key genes from the regulated pathways. Promoter sequence analysis identified over-represented transcription factor binding site (TFBS) motifs in the promoter regions of twenty two co-expressed lipid metabolism-related genes suggesting coordinated regulation of these genes by multiple transcription factors (TF). Furthermore, TF binding to these TFBS and differentially regulated in our data are annotated with nervous system development and immune response suggesting possible co-regulation of lipid metabolism, nervous system development and stress response genes. Gene expression changes in our data are consistent with pathological characteristics observed in DN including axon degeneration and demyelination, and support existing hypotheses regarding hyperglycemia mediated nerve damage in DN. Our findings support the role of hyperglycemia-induced oxidative stress and ischemia in nerve injury. Our results also support the hypothesis of oxidized lipid-mediated nerve injury and increased mitochondrial oxidative stress in dyslipidemia. Moreover, our analyses revealed a possible co-regulation mechanism connecting hyperlipidemia, stress response and axonal degeneration. Microarray data for 24 week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes
2011-02-18 | E-GEOD-27382 | biostudies-arrayexpress
Project description:A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve. Microarray data for 24 week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further used for functional enrichment analysis and network analysis to identify biological processes and pathways differentially regulated in the db/db nerve. Expression profile clustering was performed to identify co-expressed DEGs. A set of co-expressed lipid metabolism genes was used for promoter sequence analysis.We identified 4,017 DEGs; 2,122 genes were up-regulated and 1,895 genes were down-regulated in the db/db relative to the db+ samples. Over-represented biological processes identified by the functional enrichment analysis include cell cycle, lipid metabolic process, lipid transport, carbohydrate metabolic process, response to stress, apoptosis, axonogenesis and cell adhesion. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, PPAR signaling, apoptosis, and axon guidance. The majority of DEGs in the glycolysis, TCA cycle, oxidative phosphorylation, fatty acid metabolism, glycerolipid metabolism, mitochondrial fatty acid elongation, lipid transport, adipocytokine signaling, PPAR signaling, and apoptosis pathways are up-regulated, whereas most of the axonogenesis-related genes are down-regulated in db/db nerve. A network of DEGs based on their co-citation in literature identified regulatory relationship between Tnf-α and key genes from the regulated pathways. Promoter sequence analysis identified over-represented transcription factor binding site (TFBS) motifs in the promoter regions of twenty two co-expressed lipid metabolism-related genes suggesting coordinated regulation of these genes by multiple transcription factors (TF). Furthermore, TF binding to these TFBS and differentially regulated in our data are annotated with nervous system development and immune response suggesting possible co-regulation of lipid metabolism, nervous system development and stress response genes. Gene expression changes in our data are consistent with pathological characteristics observed in DN including axon degeneration and demyelination, and support existing hypotheses regarding hyperglycemia mediated nerve damage in DN. Our findings support the role of hyperglycemia-induced oxidative stress and ischemia in nerve injury. Our results also support the hypothesis of oxidized lipid-mediated nerve injury and increased mitochondrial oxidative stress in dyslipidemia. Moreover, our analyses revealed a possible co-regulation mechanism connecting hyperlipidemia, stress response and axonal degeneration.
2011-02-18 | GSE27382 | GEO
Project description:db/db mouse kidney given liraglutide or insulin compared to db/db vehicle and healthy vehicle, 12 weeks dosing, all included db/db mice over 16 mM blood glucose level.
2017-03-29 | PXD002988 | Pride
Project description:The mechanisms of diabetic neuropathy (DN) development and progression are not fully understood. We examined global gene expression in the sciatic nerve (SCN) of BKS-db/db mice at 8 and 24 weeks of age to identify genetic pathways altered in peripheral nerves at early and advanced stages of DN. The sets of differentially expressed genes were analyzed to identify enriched biological functions and regulated genetic pathways. Our results suggest that carbohydrate metabolism and lipid metabolism pathways are dysregulated in the db/db SCN at 8 weeks of age. Impairment of Schwann cell-extracellular matrix interaction and axon guidance occurs early in the development of DN, while neurotrophic support, neurotransmitter transport and axonogenesis are impaired at the advanced stage of DN. Gene expression changes also suggest that oxidative stress- and inflammation-mediated nerve damage occurs by 8 weeks. Our analysis identified mechanisms regulated in the early stages of DN. Additionally, interactions between genes from different pathways provide insight into potential relationships among the regulated pathways. RNA extracted from the SCN of four groups of mice: (8 week old db/db (n=8) or db/+ (n=8), and 24 week old db/db (n=6) or db/+ (n=7)) was hybridized to Affymetrix GeneChip microarrays. Gene expression for the two genotypes (db/db vs. db/+) was compared at each age. Gene expression at the early and advanced stages of DN (8 weeks vs. 24 weeks) was also compared for each genotype.
2012-01-06 | E-GEOD-34889 | biostudies-arrayexpress
Project description:Plasma, kidney, sciatic nerve, and retina samples collected from control (db/m) and diabetic (db/db) mice. Samples snap frozen and stored at -80. Plasma volume measured and tissues weighed for lipid extraction.
2018-08-02 | MSV000082729 | GNPS
Project description:Investigation of gene expression level changes in pancreatic and liver tissues of diabetic db/db mice supplemented with selenate, compared to the diabetic db/db mice administered placebo. Fasting blood glucose levels increased continuously in diabetic db/db mice administered placebo (DMCtrl) but decreased gradually in selenate-supplemented diabetic db/db mice (DMSe) and approached normal values when the experiment ended. The size of pancreatic islets increased, causing the plasma insulin concentration to double in DMSe mice compared with that in DMCtrl mice.
2014-03-07 | GSE55636 | GEO
Project description:Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood glucose levels in leptin receptor deficient (db/db) obese mice on a C57BL/6×C57BLKS mixed genetic background. Furthermore, shRNA mediated reduction of Aqp9 expression reduces liver triacylglycerol (TAG) accumulation in a diet induced rat model of obesity. The aim of this study was to investigate metabolic effects of Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9wt db/db and Aqp9-/- db/db mice did not differ in body weight and liver TAG contents. On the C57BL/6 genetic background we observed elevated plasma glucose in Aqp9-/- db/db mice (+ 1.1 mM, life-time average) while plasma insulin concentration was reduced at time of death. Glucose levels changed similarly in pentobarbital anesthetized, glucagon challenged Aqp9wt db/db and Aqp9-/- db/db mice. Liver transcriptional profiling did not detect differential gene expression between genotypes. Metabolite profiling revealed a sex independent increase in plasma glycerol (+55%), glucose (+24%) and reduction in threonate (all at q<0.1) in Aqp9-/- db/db mice compared to controls. Metabolite profiling thus confirms a role of AQP9 in glycerol metabolism of obese C57BL/6 db/db mice. In this animal model of obesity Aqp9 gene deletion elevates plasma glucose and does not alleviate hepatosteatosis.
2015-09-28 | MTBLS219 | MetaboLights
Project description:The mechanisms of diabetic neuropathy (DN) development and progression are not fully understood. We examined global gene expression in the sciatic nerve (SCN) of BKS-db/db mice at 8 and 24 weeks of age to identify genetic pathways altered in peripheral nerves at early and advanced stages of DN. The sets of differentially expressed genes were analyzed to identify enriched biological functions and regulated genetic pathways. Our results suggest that carbohydrate metabolism and lipid metabolism pathways are dysregulated in the db/db SCN at 8 weeks of age. Impairment of Schwann cell-extracellular matrix interaction and axon guidance occurs early in the development of DN, while neurotrophic support, neurotransmitter transport and axonogenesis are impaired at the advanced stage of DN. Gene expression changes also suggest that oxidative stress- and inflammation-mediated nerve damage occurs by 8 weeks. Our analysis identified mechanisms regulated in the early stages of DN. Additionally, interactions between genes from different pathways provide insight into potential relationships among the regulated pathways.
2012-01-06 | GSE34889 | GEO