A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue

Abstract To explore novel molecular mechanisms underlying obesity, we applied a systems genetics framework to integrate risk genetic loci from the largest body mass index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and microRNA profiling in adipose tissue from 200 subjects....

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Autores principales:	Hao He, Dianjianyi Sun, Yong Zeng, Ruifeng Wang, Wei Zhu, Shaolong Cao, George A. Bray, Wei Chen, Hui Shen, Frank M. Sacks, Lu Qi, Hong-wen Deng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6677ae389d394f33b662b0d26d85f572
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spelling	oai:doaj.org-article:6677ae389d394f33b662b0d26d85f5722021-12-02T15:05:20ZA Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue10.1038/s41598-017-01517-62045-2322https://doaj.org/article/6677ae389d394f33b662b0d26d85f5722017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01517-6https://doaj.org/toc/2045-2322Abstract To explore novel molecular mechanisms underlying obesity, we applied a systems genetics framework to integrate risk genetic loci from the largest body mass index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and microRNA profiling in adipose tissue from 200 subjects. One module was identified to be most significantly associated with obesity and other metabolic traits. We identified eight hub genes which likely play important roles in obesity metabolism and identified microRNAs that significantly negatively correlated with hub genes. This module was preserved in other three test gene expression datasets, and all hub genes were consistently downregulated in obese subjects through the meta-analysis. Gene GPD1L had the highest connectivity and was identified a key causal regulator in the module. Gene GPD1L was significantly negatively correlated with the expression of miR-210, which was experimentally validated that miR-210 regulated GPD1L protein level through direct interaction with its mRNA three prime untranslated region (3′-UTR). GPD1L was found to be upregulated during weight loss and weight maintenance induced by low calorie diet (LCD), while downregulated during weight gain induced by high-fat diet (HFD). The results indicated that increased GPD1L in adipose tissue may have a significant therapeutic potential in reducing obesity and insulin resistance.Hao HeDianjianyi SunYong ZengRuifeng WangWei ZhuShaolong CaoGeorge A. BrayWei ChenHui ShenFrank M. SacksLu QiHong-wen DengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hao He Dianjianyi Sun Yong Zeng Ruifeng Wang Wei Zhu Shaolong Cao George A. Bray Wei Chen Hui Shen Frank M. Sacks Lu Qi Hong-wen Deng A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
description	Abstract To explore novel molecular mechanisms underlying obesity, we applied a systems genetics framework to integrate risk genetic loci from the largest body mass index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and microRNA profiling in adipose tissue from 200 subjects. One module was identified to be most significantly associated with obesity and other metabolic traits. We identified eight hub genes which likely play important roles in obesity metabolism and identified microRNAs that significantly negatively correlated with hub genes. This module was preserved in other three test gene expression datasets, and all hub genes were consistently downregulated in obese subjects through the meta-analysis. Gene GPD1L had the highest connectivity and was identified a key causal regulator in the module. Gene GPD1L was significantly negatively correlated with the expression of miR-210, which was experimentally validated that miR-210 regulated GPD1L protein level through direct interaction with its mRNA three prime untranslated region (3′-UTR). GPD1L was found to be upregulated during weight loss and weight maintenance induced by low calorie diet (LCD), while downregulated during weight gain induced by high-fat diet (HFD). The results indicated that increased GPD1L in adipose tissue may have a significant therapeutic potential in reducing obesity and insulin resistance.
format	article
author	Hao He Dianjianyi Sun Yong Zeng Ruifeng Wang Wei Zhu Shaolong Cao George A. Bray Wei Chen Hui Shen Frank M. Sacks Lu Qi Hong-wen Deng
author_facet	Hao He Dianjianyi Sun Yong Zeng Ruifeng Wang Wei Zhu Shaolong Cao George A. Bray Wei Chen Hui Shen Frank M. Sacks Lu Qi Hong-wen Deng
author_sort	Hao He
title	A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
title_short	A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
title_full	A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
title_fullStr	A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
title_full_unstemmed	A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
title_sort	systems genetics approach identified gpd1l and its molecular mechanism for obesity in human adipose tissue
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6677ae389d394f33b662b0d26d85f572
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A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue

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