Cargando…

A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes

OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-...

Descripción completa

Detalles Bibliográficos
Autores principales: Gottmann, Pascal, Ouni, Meriem, Saussenthaler, Sophie, Roos, Julian, Stirm, Laura, Jähnert, Markus, Kamitz, Anne, Hallahan, Nicole, Jonas, Wenke, Fritsche, Andreas, Häring, Hans-Ulrich, Staiger, Harald, Blüher, Matthias, Fischer-Posovszky, Pamela, Vogel, Heike, Schürmann, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001404/
https://www.ncbi.nlm.nih.gov/pubmed/29605715
http://dx.doi.org/10.1016/j.molmet.2018.03.005
_version_ 1783331991852154880
author Gottmann, Pascal
Ouni, Meriem
Saussenthaler, Sophie
Roos, Julian
Stirm, Laura
Jähnert, Markus
Kamitz, Anne
Hallahan, Nicole
Jonas, Wenke
Fritsche, Andreas
Häring, Hans-Ulrich
Staiger, Harald
Blüher, Matthias
Fischer-Posovszky, Pamela
Vogel, Heike
Schürmann, Annette
author_facet Gottmann, Pascal
Ouni, Meriem
Saussenthaler, Sophie
Roos, Julian
Stirm, Laura
Jähnert, Markus
Kamitz, Anne
Hallahan, Nicole
Jonas, Wenke
Fritsche, Andreas
Häring, Hans-Ulrich
Staiger, Harald
Blüher, Matthias
Fischer-Posovszky, Pamela
Vogel, Heike
Schürmann, Annette
author_sort Gottmann, Pascal
collection PubMed
description OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line. RESULTS: In 17 partially overlapping QTL for obesity and T2D 170 miRNAs were identified. Four miRNAs (miR-15b, miR-30b, miR-31, miR-744) were recognized in gWAT (gonadal white adipose tissue) and six (miR-491, miR-455, miR-423-5p, miR-132-3p, miR-365-3p, miR-30b) in BAT (brown adipose tissue). To provide direct functional evidence for the achievement of the miR-QTL-Scan, miR-31 located in the obesity QTL Nob6 was experimentally analyzed. Its expression was higher in gWAT of obese and diabetic mice and humans than of lean controls. Accordingly, 10 potential target genes involved in insulin signaling and adipogenesis were suppressed. Manipulation of miR-31 in human SGBS adipocytes affected the expression of GLUT4, PPARγ, IRS1, and ACACA. In human peripheral blood mononuclear cells (PBMC) miR-15b levels were correlated to baseline blood glucose concentrations and might be an indicator for diabetes. CONCLUSION: Thus, miR-QTL-Scan allowed the identification of novel miRNAs relevant for obesity and T2D.
format Online
Article
Text
id pubmed-6001404
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-60014042018-06-15 A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes Gottmann, Pascal Ouni, Meriem Saussenthaler, Sophie Roos, Julian Stirm, Laura Jähnert, Markus Kamitz, Anne Hallahan, Nicole Jonas, Wenke Fritsche, Andreas Häring, Hans-Ulrich Staiger, Harald Blüher, Matthias Fischer-Posovszky, Pamela Vogel, Heike Schürmann, Annette Mol Metab Original Article OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line. RESULTS: In 17 partially overlapping QTL for obesity and T2D 170 miRNAs were identified. Four miRNAs (miR-15b, miR-30b, miR-31, miR-744) were recognized in gWAT (gonadal white adipose tissue) and six (miR-491, miR-455, miR-423-5p, miR-132-3p, miR-365-3p, miR-30b) in BAT (brown adipose tissue). To provide direct functional evidence for the achievement of the miR-QTL-Scan, miR-31 located in the obesity QTL Nob6 was experimentally analyzed. Its expression was higher in gWAT of obese and diabetic mice and humans than of lean controls. Accordingly, 10 potential target genes involved in insulin signaling and adipogenesis were suppressed. Manipulation of miR-31 in human SGBS adipocytes affected the expression of GLUT4, PPARγ, IRS1, and ACACA. In human peripheral blood mononuclear cells (PBMC) miR-15b levels were correlated to baseline blood glucose concentrations and might be an indicator for diabetes. CONCLUSION: Thus, miR-QTL-Scan allowed the identification of novel miRNAs relevant for obesity and T2D. Elsevier 2018-03-15 /pmc/articles/PMC6001404/ /pubmed/29605715 http://dx.doi.org/10.1016/j.molmet.2018.03.005 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Gottmann, Pascal
Ouni, Meriem
Saussenthaler, Sophie
Roos, Julian
Stirm, Laura
Jähnert, Markus
Kamitz, Anne
Hallahan, Nicole
Jonas, Wenke
Fritsche, Andreas
Häring, Hans-Ulrich
Staiger, Harald
Blüher, Matthias
Fischer-Posovszky, Pamela
Vogel, Heike
Schürmann, Annette
A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes
title A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes
title_full A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes
title_fullStr A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes
title_full_unstemmed A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes
title_short A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes
title_sort computational biology approach of a genome-wide screen connected mirnas to obesity and type 2 diabetes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001404/
https://www.ncbi.nlm.nih.gov/pubmed/29605715
http://dx.doi.org/10.1016/j.molmet.2018.03.005
work_keys_str_mv AT gottmannpascal acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT ounimeriem acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT saussenthalersophie acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT roosjulian acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT stirmlaura acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT jahnertmarkus acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT kamitzanne acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT hallahannicole acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT jonaswenke acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT fritscheandreas acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT haringhansulrich acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT staigerharald acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT bluhermatthias acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT fischerposovszkypamela acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT vogelheike acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT schurmannannette acomputationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT gottmannpascal computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT ounimeriem computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT saussenthalersophie computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT roosjulian computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT stirmlaura computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT jahnertmarkus computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT kamitzanne computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT hallahannicole computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT jonaswenke computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT fritscheandreas computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT haringhansulrich computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT staigerharald computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT bluhermatthias computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT fischerposovszkypamela computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT vogelheike computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes
AT schurmannannette computationalbiologyapproachofagenomewidescreenconnectedmirnastoobesityandtype2diabetes