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Open Access 01-12-2015 | Research article

Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis

Authors: Alain Veilleux, Sylvain Mayeur, Jean-Christophe Bérubé, Jean-François Beaulieu, Eric Tremblay, Frédéric-Simon Hould, Yohan Bossé, Denis Richard, Emile Levy

Published in: BMC Gastroenterology | Issue 1/2015

Abstract

Background

Metabolic alterations relevant to postprandial dyslipidemia were previously identified in the intestine of obese insulin-resistant subjects. The aim of the study was to identify the genes deregulated by systemic insulin resistance in the intestine of severely obese subjects.

Methods

Transcripts from duodenal samples of insulin-sensitive (HOMA-IR < 3, n = 9) and insulin-resistant (HOMA-IR > 7, n = 9) obese subjects were assayed by microarray (Illumina HumanHT-12).

Results

A total of 195 annotated genes were identified as differentially expressed between these two groups (Fold change > 1.2). Of these genes, 36 were found to be directly involved in known intestinal functions, including digestion, extracellular matrix, endocrine system, immunity and cholesterol metabolism. Interestingly, all differentially expressed genes (n = 8) implicated in inflammation and oxidative stress were found to be upregulated in the intestine of insulin-resistant compared to insulin-sensitive subjects. Metabolic pathway analysis revealed that several signaling pathways involved in immunity and inflammation were significantly enriched in differently expressed genes and were predicted to be activated in the intestine of insulin-resistant subjects. Using stringent criteria (Fold change > 1.5; FDR < 0.05), three genes were found to be significantly and differently expressed in the intestine of insulin-resistant compared to insulin-sensitive subjects: the transcripts of the insulinotropic glucose-dependant peptide (GIP) and of the β-microseminoprotein (MSMB) were significantly reduced, but that of the humanin like-1 (MTRNR2L1) was significantly increased.

Conclusion

These results underline that systemic insulin resistance is associated with remodeling of key intestinal functions. Moreover, these data indicate that small intestine metabolic dysfunction is accompanied with a local amplification of low-grade inflammatory process implicating several pathways. Genes identified in this study are potentially triggered throughout the development of intestinal metabolic abnormalities, which could contribute to dyslipidemia, a component of metabolic syndrome and diabetes.

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Title: Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis
Authors: Alain Veilleux
Sylvain Mayeur
Jean-Christophe Bérubé
Jean-François Beaulieu
Eric Tremblay
Frédéric-Simon Hould
Yohan Bossé
Denis Richard
Emile Levy
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Gastroenterology / Issue 1/2015
Electronic ISSN: 1471-230X
DOI: https://doi.org/10.1186/s12876-015-0342-y

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Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis

Abstract

Background

Methods

Results

Conclusion

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