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Gene expression data from adipocytes of insulin resistant mice

ABSTRACT: We developed a novel network inference approach, Biologically Anchored Knowledge Expansion (BAKE), to analyze large volume gene expression data obtained from a mouse model of insulin resistance progression. Both genetic aspects and dietary factors, specifically high caloric high-fat high-sugar diets, contribute to the progression of insulin resistance. To mimic genetic predisposition, we used a mouse model with double heterozygous deletion of early insulin signaling pathway intermediates, insulin receptor (IR) and insulin receptor substrate 1 (IRS1) genes. These mice were fed with high-fat (Western) or low-fat (Chow) diet for 8 and 16 weeks starting at 8 weeks of age. Gene expression data was collected from adipocytes isolated from these mice. Applying BAKE analysis to the adipocyte gene expression data, we demonstrate that we can accurately discover a novel regulatory gene in the insulin signaling pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE76428 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA307265

REPOSITORIES: GEO

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Project description:High fat diet (HFD) during early development may increase the susceptibility to metabolic diseases later in life. Adipose tissue is an important regulator of energy metabolism through secretion of endocrine and paracrine/autocrine factors. In the present study we first screened the expression profiles of about 500 miRNAs in visceral white adipose tissue (VAT) from mice fed a control diet (CD) and mice fed a matched HFD during three different life stages i) in utero (UT), ii) in utero and lactation (UL), iii) in utero until termination at age 23 weeks (WL). Fourteen differentially expressed miRNAs were identified and these miRNAs were used for prediction of targeted signalling pathways. In addition, analysis of high abundance miRNAs showed a marked downregulation of the miR-200 family members in the UT group. Subsequently, the transcript levels of 89 selected genes represented in the predicted signalling pathways were determined. Six genes (Deptor, Il6, Irs1, lep, Lpin1 and prkaa1) showed a significant differential expression due to HFD feeding compared to controls, and HFD treatment had significant effects on the WL-groups. The expression pattern of Deptor, Il6, Irs1, Lep genes showed a similar direction of change across all HFD treatment groups. The differential expression of Irs1 and Deptor genes points to a persistent modification of the insulin receptor – mTOR signalling network. This finding is supported by increased serum insulin and IGF-1 levels and impaired glucose regulation in the HFD groups. This study shows that developmental HFD can lead to persistent changes in VAT miRNA expression levels that is associated with a modification of key signalling pathways regulating energy metabolism also in animals with normal BMI.dy we have screened over 500 miRNAs for differential expression in visceral white adipose tissue (vWAT) between mice fed a control diet (CD; 10% kcal from fat) and mice fed a matched high fat diet (HFD; 45% kcal from fat) during three different life stages i) in utero (UT), ii) in utero and lactation (UL), iii) in utero until termination (WL). All animals were sacrifices at an age of 23 weeks.

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Gene expression data from adipocytes of insulin resistant mice

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