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Differential expression of genes in pancreatic islets from high fat fed AKR/J and C57Bl/6J

ABSTRACT: Increased fat intake is associated with obesity and insulin resistance. In some individuals, a failure of pancreatic b-cells to increase insulin production in response to the high demands of obesity leads to diabetes. We sought to determine whether the impaired b- cell adaptation in obesity is associated with differential expression of genes involved in b-cell expansion and intermediary metabolism. Two strains of inbred mice prone to obesity, C57Bl/6J and AKR/J, were fed regular rodent chow or high-fat diet, after which islet morphology, secretory function and gene expression were assessed. AKR/J had lower blood glucose and higher insulin levels compared with C57Bl/6J mice on regular rodent chow or high fat diet. Insulin secretion was 3.2 fold higher in AKR/J than C57Bl/6J mice following intraperitoneal glucose injection. Likewise, glucose-stimulated insulin secretion from isolated islets was higher in AKR/J. Additionally, islet mass was 1.4 fold greater in AKR/J compared with C57Bl/6J. To elucidate the factors associated with the differences in insulin, we analyzed the gene expression profiles in pancreatic islets in AKR/J and C57Bl/6J mice. Of 14,000 genes examined, 220 were up-regulated and 286 were down-regulated in islets from diet-induced obese AKR/J mice compared with C57Bl/6J mice. Key genes involved in islet signaling and metabolism, e.g. glucagon like peptide-1 receptor, sterol Co-A desaturase 1 & 2 and fatty acid desaturase 2 were upregulated in obese AKR/J mice. The expression of multiple extracellular matrix proteins was also increased in AKR/J mice, suggesting a role in modulation of islet mass. Functional analyses of differentially regulated genes hold promise for elucidating factors linking obesity to alterations in islet function. Keywords: response to high fat diet

ORGANISM(S): Mus musculus

PROVIDER: GSE10639 | GEO | 2008/02/28

SECONDARY ACCESSION(S): PRJNA107711

REPOSITORIES: GEO

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Project description:Increased fat intake is associated with obesity and insulin resistance. In some individuals, a failure of pancreatic b-cells to increase insulin production in response to the high demands of obesity leads to diabetes. We sought to determine whether the impaired b- cell adaptation in obesity is associated with differential expression of genes involved in b-cell expansion and intermediary metabolism. Two strains of inbred mice prone to obesity, C57Bl/6J and AKR/J, were fed regular rodent chow or high-fat diet, after which islet morphology, secretory function and gene expression were assessed. AKR/J had lower blood glucose and higher insulin levels compared with C57Bl/6J mice on regular rodent chow or high fat diet. Insulin secretion was 3.2 fold higher in AKR/J than C57Bl/6J mice following intraperitoneal glucose injection. Likewise, glucose-stimulated insulin secretion from isolated islets was higher in AKR/J. Additionally, islet mass was 1.4 fold greater in AKR/J compared with C57Bl/6J. To elucidate the factors associated with the differences in insulin, we analyzed the gene expression profiles in pancreatic islets in AKR/J and C57Bl/6J mice. Of 14,000 genes examined, 220 were up-regulated and 286 were down-regulated in islets from diet-induced obese AKR/J mice compared with C57Bl/6J mice. Key genes involved in islet signaling and metabolism, e.g. glucagon like peptide-1 receptor, sterol Co-A desaturase 1 & 2 and fatty acid desaturase 2 were upregulated in obese AKR/J mice. The expression of multiple extracellular matrix proteins was also increased in AKR/J mice, suggesting a role in modulation of islet mass. Functional analyses of differentially regulated genes hold promise for elucidating factors linking obesity to alterations in islet function. Experiment Overall Design: Microarray analyses were performed on quadruplicate RNA samples of pancreatic islets from AKR and Bl6 mice placed on high-fat diet for 3 months. Pancreases from two mice were combined to yield one sample of islet RNA. All protocols were conducted as described in the Affymetrix GeneChips Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA) using 5 Î¼g total RNA and GeneChip Mouse Expression Arrays MOE 430 (Affymetrix).

Project description:An 8-week high fat palm oil diet causes obesity and insulin resistance in C57BL/6J mice, but induces only small changes in the muscle transcriptome. Introduction: The metabolic syndrome (MS) is a cluster of metabolic abnormalities linked to an increased risk of type 2 diabetes and cardiovascular diseases. Two major characteristics of the MS are obesity and insulin resistance. In the present study we investigated the effect of obesity and insulin resistance on the mouse muscle transcriptome. Methods: C57BL/6J mice were fed a palm oil-based low fat diet (LFD) or high fat diet (HFD) for eight weeks. Microarray analysis was performed by using two complementary strategies: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. Results: HFD mice develop obesity and whole-body insulin resistance. Despite these metabolic disturbances we found that HFD induces relatively small changes in gene expression (< 1.3 fold). Only the up-regulation of FA oxidation and the down-regulation of the MAPK cascade were specific for the HFD intervention. Eight-weeks of aging induced more changed gene expression levels than the HFD, including genes involved in cell-cell interaction and development. Conclusion: Eight weeks of aging induce more pronounced changes in the muscle transcriptome than an HFD. Since only one strategy revealed the transcriptional down-regulation of the MAPK cascade, whereas both strategies showed the up-regulation of FA oxidation we suggest the use of complementary analysis strategies by the genome-wide search of gene expression changes induced by mild interventions, such as an HFD. Keywords: diet intervention and time course In this study, C57BL/6J mice were fed a high fat (HF) diet for 8 weeks to induce obesity and insulin resistance. Plasma levels of the adipokines leptin and adiponectin were measured. To investigate how these metabolic disturbances will influence the skeletal muscle transcriptome we performed whole-genome microarray analysis. Functional implications were assessed by analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways.

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Differential expression of genes in pancreatic islets from high fat fed AKR/J and C57Bl/6J

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