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01.06.2014 | Article | Ausgabe 6/2014

Diabetologia 6/2014

Integrative analysis reveals novel pathways mediating the interaction between adipose tissue and pancreatic islets in obesity in rats

Zeitschrift:
Diabetologia > Ausgabe 6/2014
Autoren:
Rita Malpique, Hugo Figueiredo, Yaiza Esteban, Sandra A. Rebuffat, Felicia A. Hanzu, Maria Vinaixa, Oscar Yanes, Xavier Correig, Sílvia Barceló-Batllori, Rosa Gasa, Susana G. Kalko, Ramon Gomis
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00125-014-3205-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Abstract

Aims/hypothesis

Comprehensive characterisation of the interrelation between the peripancreatic adipose tissue and the pancreatic islets promises novel insights into the mechanisms that regulate beta cell adaptation to obesity. Here, we sought to determine the main pathways and key molecules mediating the crosstalk between these two tissues during adaptation to obesity by the way of an integrated inter-tissue, multi-platform analysis.

Methods

Wistar rats were fed a standard or cafeteria diet for 30 days. Transcriptomic variations by diet in islets and peripancreatic adipose tissue were examined through microarray analysis. The secretome from peripancreatic adipose tissue was subjected to a non-targeted metabolomic and proteomic analysis. Gene expression variations in islets were integrated with changes in peripancreatic adipose tissue gene expression and protein and metabolite secretion using an integrated inter-tissue pathway and network analysis.

Results

The highest level of data integration, linking genes differentially expressed in both tissues with secretome variations, allowed the identification of significantly enriched canonical pathways, such as the activation of liver/retinoid X receptors, triacylglycerol degradation, and regulation of inflammatory and immune responses, and underscored interaction network hubs, such as cholesterol and the fatty acid binding protein 4, which were unpredicted through single-tissue analysis and have not been previously implicated in the peripancreatic adipose tissue crosstalk with beta cells.

Conclusions/interpretation

The integrated analysis reported here allowed the identification of novel mechanisms and key molecules involved in peripancreatic adipose tissue interrelation with beta cells during the development of obesity; this might help the development of novel strategies to prevent type 2 diabetes.

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Zusatzmaterial
ESM Table 1 (PDF 58 kb)
125_2014_3205_MOESM1_ESM.pdf
ESM Table 2 (PDF 79 kb)
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ESM Table 3 (PDF 68 kb)
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ESM Table 4 (PDF 32 kb)
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ESM Table 5 (PDF 31 kb)
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ESM Table 6 (PDF 52 kb)
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ESM Fig. 1 2D-DIGE differential analysis of adipose tissue secretomes from OB vs STD rats. Representative image gel evidencing the 36 spot locations selected for excision after applying the statistical analysis (Two-way ANOVA and the two-tailed Student’s T-test for paired samples, p-value<0.05). (PDF 2939 kb)
125_2014_3205_MOESM7_ESM.pdf
ESM Fig. 2 Single-tissue, single-platform pathway mapping. PM-WAT (a) and pancreatic islets (b) transcriptomics integrative pathway mapping and PM-WAT secretome proteomics (c) and metabolomics (d) integrative pathway mapping (highest score network), considering only direct interactions. (PDF 546 kb)
125_2014_3205_MOESM8_ESM.pdf
ESM Fig. 3 Inter-tissue, multi-platform integrative pathway mapping, considering only direct interactions: (a) Pancreatic transcriptomics data superimposed on the secretome metabolite network (b) Pancreatic islets transcriptomics data and PM-WAT secretome proteomics data superimposed on the PM-WAT secretome metabolite network. (PDF 386 kb)
125_2014_3205_MOESM9_ESM.pdf
ESM Fig. 4 Gene expression changes in islet immune and inflammatory response signalling due to 30 day (a) and 6 month (b) cafeteria diet-induced obesity. Real-time PCR results for statistically significant genes: black bars = STD group; white bars = OB group. The expression of each gene was normalized with the constitutive expression of the gene Gadph. All values are presented as mean ± SEM from 6 to 10 animals per group. *P < 0.05, **P < 0.01 and ***P < 0.005. (PDF 369 kb)
125_2014_3205_MOESM10_ESM.pdf
ESM Fig. 5 (PDF 22162 kb)
125_2014_3205_MOESM11_ESM.pdf
Literatur
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