首页    期刊浏览 2024年11月30日 星期六
登录注册

文章基本信息

  • 标题:A Systems Genetics Approach Identified GPD1L and its Molecular Mechanism for Obesity in Human Adipose Tissue
  • 本地全文:下载
  • 作者:Hao He ; Dianjianyi Sun ; Yong Zeng
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2017
  • 卷号:7
  • 期号:1
  • DOI:10.1038/s41598-017-01517-6
  • 语种:English
  • 出版社:Springer Nature
  • 摘要: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.
国家哲学社会科学文献中心版权所有