A diet-induced type 2 diabetes model in Drosophila
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA632829 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11789500.fastq.gz | Fastqsanger.gz | |||
| SRR11789501.fastq.gz | Fastqsanger.gz | |||
| SRR11789502.fastq.gz | Fastqsanger.gz | |||
| SRR11789503.fastq.gz | Fastqsanger.gz | |||
| SRR11789504.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:We showed in this present study that HSD feeding could induce type 2 diabetes-like phenotype in fruit flies, resembling the key disease features including hyperglycemia, glucosuria, increased hunger and thirsty, unexplained weight loss, and reduced female fecundity. We also showed that HSD-fed flies shared similar molecular mechanisms underlying type 2 diabetes patients, including both insulin deficiency and insulin resistance. Last but not least, disrupting insulin signaling in fruit flies could mimic the effect of HSD feeding to induce type 2 diabetes-like phenotype, further confirming that these phenotypes were a result of compromised insulin signaling upon HSD feeding. Taken together, we demonstrated that this diet-induced type 2 diabetes model in fruit flies rightly and comprehensively recapitulated the physiological, metabolic, behavioral, and molecular features of human type 2 diabetes, offering a valid and accessible model to study the underlying mechanism of this disease and to validate potential diagnostics and therapeutic tools. Given the highly conserved regulatory framework of physiology and metabolism between flies and human, our work has paved a way to generate novel insights into type 2 diabetes, a common, severe, and yet poorly understood disease in human.
2021-05-17 | GSE150565 | GEO
Project description:Research findings of the past decade have highlighted the gut as the main site of action of the oral antihyperglycemic agent metformin despite its pharmacological role in the liver. Extensive evidence supports metformin’s modulatory effect on the composition and function of gut microbiota, nevertheless, the underlying mechanisms of the host responses remain elusive. Our study aimed to evaluate metformin-induced alterations in the intestinal transcriptome profiles at different metabolic states. The high-fat diet-induced type 2 diabetes mouse model of both sexes was developed in a randomized block experiment and bulk RNA-Seq of the ileum tissue was the method of choice for comparative transcriptional profiling after metformin intervention for ten weeks. We found a prominent transcriptional effect of the diet itself with comparatively fewer genes responding to metformin intervention. The overrepresentation of immune-related genes was observed, including pronounced metformin-induced upregulation of immunoglobulin heavy-chain variable regioncoding Ighv1-7 gene in both high-fat diet and control diet-fed animals, supporting the contribution of intestinal immunoglobulin responses. Finally, we provide evidence of the downregulation NF-kappa B signaling pathway in the small intestine of both hyperglycemic and normoglycemic animals after metformin treatment. Moreover, our data pinpoint the gut microbiota as a crucial component in the metformin-mediated downregulation of NF-kappaB signaling evidenced by a positive correlation between the Rel and Rela gene expression levels and abundances of Parabacteroides distasonis, Bacteroides spp., and Lactobacillus spp. in the gut microbiota of the same animals.
2023-08-12 | GSE240206 | GEO
Project description:Transcriptomic profiling in a Drosophila model of diet induced transgenerational epigenetic inheritance.
| PRJNA490729 | ENA
Project description:Aortic endothelia from mice exposed to dietary model of type II diabetes at 4, 6 and 8 weeks of exposure to Bio-Serv #S3282 diet. Objective: Type II diabetes is associated with endothelial dysfunction, which can contribute to accelerated atherosclerosis and subsequent cardiovascular events. We seek to identify transcripts dysregulated in vivo in response to chronic exposure to high dietary fat that leads to diabetes. Methods: Beginning at 8 weeks of age, male Tie2-GFP mice (transgenically expressing green fluorescent protein exclusively within the endothelia) were fed a 60% fat calorie diet (Bio-Serv #S3282); age-matched mice were fed normal chow. After 4, 6, and 8 weeks on the diet, aortae and skeletal muscles (gastrocnemius, biceps femoris, and plantaris) were excised, minced, and collagenolytically digested. Each tissue digest was then subjected to FACS in order to obtain 10,000 endothelial cells. Transcriptomic analyses were performed with microarrays containing the Operon Murine V4 oligo set, and highly dysregulated genes were confirmed by real-time PCR. Results: By 4 weeks, Tie2-GFP mice receiving a high fat diet exhibited a fasting glucose of 215+17 mg/dL vs. 134+23 mg/dL in controls; by 6 weeks, a high fat diet resulted in lower glucose tolerance vs. control diet. Following 4, 6, and 8 weeks of high-fat regimen, aortic endothelial transcripts up-regulated by greater than 2-fold in biologically replicate experiments included macrophage inflammatory protein 2 (Mip2), chemokine (C-C motif) ligand 9 (CCL9), galectin-3 (Gal-3), and 5-lipoxygenase-activating protein (FLAP). Endothelial transcripts up-regulated in skeletal muscle included Mip2, CCL8 and 9, FLAP, gal-1 and 3, and ferritin light chain 1 (FTL1); transcripts down-regulated in muscle included endothelin-1 (ET-1) and insulin-like growth factor II (IGF II). Discussion: Gal-3 and FTL-1 are known to increase in response to advanced glycation end-products and oxidized LDL, respectively. However, the down-regulation of ET-1 and IGFII was surprising, as the transcription of these genes has previously been thought to exacerbate atherosclerosis. In conclusion, a comprehensive analysis of the endothelial transcript-level response to a dietary model of Type II diabetes has revealed novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Understanding the mechanism of diabetes-associated endothelial dysfunction may lead to improved therapies that lower the risk of cardiovascular complications in diabetic patients. Each experiment is performed with a technical replicate i.e. dye reversal. there is a biological replicate of the 4 week time point
2009-03-27 | E-GEOD-14898 | biostudies-arrayexpress
Project description:Epidemiological surveys first indicated that obesity and type II diabetes generated by lipid rich diets may be efficiently inherited, both paternally and maternally. This apparent exception to the fundamental law of non heritability of acquired characters was more recently documented in laboratory organisms but the transgenerational signal remained a matter of speculation. Here we show that experimental transfer to healthy one-cell embryos of testis RNA prepared from males raised on high-fat-diet (HFD) results in the development of obesity and diabetes in the adult. Body weight, fasting glucose levels, response to insulin, glucose tolerance, RNA levels of leptin and stearoyl-CoA desaturase were all affected in mice born after RNA microinjection to the same extent as in the progenitors and in their sexual offspring. Surprisingly, neither microarray hybridization nor deep sequencing of the inducer and control RNAs showed a differential expression of known regulators of adipogenesis, but only modest variations in a series of transcripts. Transgenerational maintenance appears as one instance of the RNA-mediated heredity of epigenetic traits previously demonstrated in experimental systems ranging from the worm to the mouse. The relationship between lipid-rich diet and changes in testicular RNAs on one side and the nature of the mark imprinted on the one-cell embryo by RNA transfer and responsible for pathological developments at later stages are questions of interest for future studies. Two experimental groups composed of four individuals. Controls = M1N,M2N,TN1,TN2 and Experimentals= M1W,M2W,M3W,M5W.
2014-01-16 | E-GEOD-43555 | biostudies-arrayexpress
Project description:Transcriptomic analysis of peripheral neuropathy in a high-fat diet-induced mouse model of type 2 diabetes
| PRJNA934372 | ENA
Project description:Metformin Targets Intestinal Immune System Signaling Pathways in High-Fat Diet-Induced Type 2 Diabetes Mouse Model
| PRJNA1002964 | ENA
Project description:Aortic endothelia from mice exposed to dietary model of type II diabetes at 4, 6 and 8 weeks of exposure to Bio-Serv #S3282 diet. Objective: Type II diabetes is associated with endothelial dysfunction, which can contribute to accelerated atherosclerosis and subsequent cardiovascular events. We seek to identify transcripts dysregulated in vivo in response to chronic exposure to high dietary fat that leads to diabetes. Methods: Beginning at 8 weeks of age, male Tie2-GFP mice (transgenically expressing green fluorescent protein exclusively within the endothelia) were fed a 60% fat calorie diet (Bio-Serv #S3282); age-matched mice were fed normal chow. After 4, 6, and 8 weeks on the diet, aortae and skeletal muscles (gastrocnemius, biceps femoris, and plantaris) were excised, minced, and collagenolytically digested. Each tissue digest was then subjected to FACS in order to obtain 10,000 endothelial cells. Transcriptomic analyses were performed with microarrays containing the Operon Murine V4 oligo set, and highly dysregulated genes were confirmed by real-time PCR. Results: By 4 weeks, Tie2-GFP mice receiving a high fat diet exhibited a fasting glucose of 215+17 mg/dL vs. 134+23 mg/dL in controls; by 6 weeks, a high fat diet resulted in lower glucose tolerance vs. control diet. Following 4, 6, and 8 weeks of high-fat regimen, aortic endothelial transcripts up-regulated by greater than 2-fold in biologically replicate experiments included macrophage inflammatory protein 2 (Mip2), chemokine (C-C motif) ligand 9 (CCL9), galectin-3 (Gal-3), and 5-lipoxygenase-activating protein (FLAP). Endothelial transcripts up-regulated in skeletal muscle included Mip2, CCL8 and 9, FLAP, gal-1 and 3, and ferritin light chain 1 (FTL1); transcripts down-regulated in muscle included endothelin-1 (ET-1) and insulin-like growth factor II (IGF II). Discussion: Gal-3 and FTL-1 are known to increase in response to advanced glycation end-products and oxidized LDL, respectively. However, the down-regulation of ET-1 and IGFII was surprising, as the transcription of these genes has previously been thought to exacerbate atherosclerosis. In conclusion, a comprehensive analysis of the endothelial transcript-level response to a dietary model of Type II diabetes has revealed novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Understanding the mechanism of diabetes-associated endothelial dysfunction may lead to improved therapies that lower the risk of cardiovascular complications in diabetic patients.
2009-03-28 | GSE14898 | GEO
Project description:Epidemiological surveys first indicated that obesity and type II diabetes generated by lipid rich diets may be efficiently inherited, both paternally and maternally. This apparent exception to the fundamental law of non heritability of acquired characters was more recently documented in laboratory organisms but the transgenerational signal remained a matter of speculation. Here we show that experimental transfer to healthy one-cell embryos of testis RNA prepared from males raised on high-fat-diet (HFD) results in the development of obesity and diabetes in the adult. Body weight, fasting glucose levels, response to insulin, glucose tolerance, RNA levels of leptin and stearoyl-CoA desaturase were all affected in mice born after RNA microinjection to the same extent as in the progenitors and in their sexual offspring. Surprisingly, neither microarray hybridization nor deep sequencing of the inducer and control RNAs showed a differential expression of known regulators of adipogenesis, but only modest variations in a series of transcripts. Transgenerational maintenance appears as one instance of the RNA-mediated heredity of epigenetic traits previously demonstrated in experimental systems ranging from the worm to the mouse. The relationship between lipid-rich diet and changes in testicular RNAs on one side and the nature of the mark imprinted on the one-cell embryo by RNA transfer and responsible for pathological developments at later stages are questions of interest for future studies.
2014-01-16 | GSE43555 | GEO
Project description:Peripheral neuropathy (PN) is the most common microvascular complication of type 2 diabetes mellitus (T2D). However, a thorough understanding of the mechanisms underlying PN pathogenesis is currently lacking. Thus, the goal of the current study was to use system biology approaches to investigate the development and progression of PN in a high-fat diet (HFD)-induced mouse model of T2D. Transcriptomic data sets from sciatic nerve (SCN) and dorsal root ganglia (DRG) tissue were collected from 12- and 36-week-old HFD-fed mice and analyzed using self-organizing map and differentially expressed gene analysis with functional enrichment. Consistent with prior literature, pathways related to immune function and inflammation, mTOR signaling, and lipid metabolism were dysregulated in the SCN and DRG of HFD-fed mice. Additionally, cell-type abundance analysis revealed changes in cell composition in the SCN and DRG of HFD-fed T2D mice over time, particularly in the SCN. Comparison of differentially expressed genes from the SCN of HFD-fed mice to transcriptomic data from human sural nerve further supported the role of inflammation, mTOR signaling, and lipid metabolism in PN. Results from this study provide the basis for mechanistic studies investigating nerve damage in T2D and support the development of mechanism-based treatment options for PN.
2024-06-20 | GSE225224 | GEO