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-...
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Elsevier
2018-05-01
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Series: | Molecular Metabolism |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877818301315 |
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doaj-b43f895593b3447b9e47be298c257584 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pascal Gottmann Meriem Ouni Sophie Saussenthaler Julian Roos Laura Stirm Markus Jähnert Anne Kamitz Nicole Hallahan Wenke Jonas Andreas Fritsche Hans-Ulrich Häring Harald Staiger Matthias Blüher Pamela Fischer-Posovszky Heike Vogel Annette Schürmann |
spellingShingle |
Pascal Gottmann Meriem Ouni Sophie Saussenthaler Julian Roos Laura Stirm Markus Jähnert Anne Kamitz Nicole Hallahan Wenke Jonas Andreas Fritsche Hans-Ulrich Häring Harald Staiger Matthias Blüher Pamela Fischer-Posovszky Heike Vogel Annette Schürmann A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetes Molecular Metabolism |
author_facet |
Pascal Gottmann Meriem Ouni Sophie Saussenthaler Julian Roos Laura Stirm Markus Jähnert Anne Kamitz Nicole Hallahan Wenke Jonas Andreas Fritsche Hans-Ulrich Häring Harald Staiger Matthias Blüher Pamela Fischer-Posovszky Heike Vogel Annette Schürmann |
author_sort |
Pascal Gottmann |
title |
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_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_sort |
computational biology approach of a genome-wide screen connected mirnas to obesity and type 2 diabetes |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2018-05-01 |
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. Keywords: QTL, Computational biology, Insulin signalling, miR-31, Adipogenesis, Type 2 diabetes |
url |
http://www.sciencedirect.com/science/article/pii/S2212877818301315 |
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doaj-b43f895593b3447b9e47be298c2575842020-11-24T20:59:59ZengElsevierMolecular Metabolism2212-87782018-05-0111145159A computational biology approach of a genome-wide screen connected miRNAs to obesity and type 2 diabetesPascal Gottmann0Meriem Ouni1Sophie Saussenthaler2Julian Roos3Laura Stirm4Markus Jähnert5Anne Kamitz6Nicole Hallahan7Wenke Jonas8Andreas Fritsche9Hans-Ulrich Häring10Harald Staiger11Matthias Blüher12Pamela Fischer-Posovszky13Heike Vogel14Annette Schürmann15German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075, Ulm, GermanyGerman Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard Karls University Tübingen, 72076, Tübingen, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard Karls University Tübingen, 72076, Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Angiology, and Clinical Chemistry, University Hospital Tübingen, 72076, Tübingen, GermanyGerman Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard Karls University Tübingen, 72076, Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Angiology, and Clinical Chemistry, University Hospital Tübingen, 72076, Tübingen, GermanyGerman Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard Karls University Tübingen, 72076, Tübingen, Germany; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, 72076, Tübingen, GermanyDepartment of Medicine, University of Leipzig, 04103, Leipzig, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075, Ulm, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, GermanyGerman Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany; Corresponding author. German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, Arthur-Scheunert-Allee 114-116, D-14558, Nuthetal, Germany.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. Keywords: QTL, Computational biology, Insulin signalling, miR-31, Adipogenesis, Type 2 diabeteshttp://www.sciencedirect.com/science/article/pii/S2212877818301315 |