Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats
Around 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat pr...
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Frontiers Media S.A.
2020-11-01
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Series: | Frontiers in Endocrinology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2020.565858/full |
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doaj-6b91026c2d5d470dbaaef4d39ce1f9f1 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chengdong Xia Xiuli Zhang Xiuli Zhang Xiuli Zhang Tianshu Cao Jiannong Wang Cuidan Li Cuidan Li Liya Yue Liya Yue Kaifeng Niu Kaifeng Niu Yicheng Shen Yicheng Shen Yicheng Shen Guannan Ma Guannan Ma Fei Chen Fei Chen Fei Chen |
spellingShingle |
Chengdong Xia Xiuli Zhang Xiuli Zhang Xiuli Zhang Tianshu Cao Jiannong Wang Cuidan Li Cuidan Li Liya Yue Liya Yue Kaifeng Niu Kaifeng Niu Yicheng Shen Yicheng Shen Yicheng Shen Guannan Ma Guannan Ma Fei Chen Fei Chen Fei Chen Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats Frontiers in Endocrinology type 2 diabetes mellitus (T2DM) molecular pathogenesis substance metabolism inflammation liver injury ER stress |
author_facet |
Chengdong Xia Xiuli Zhang Xiuli Zhang Xiuli Zhang Tianshu Cao Jiannong Wang Cuidan Li Cuidan Li Liya Yue Liya Yue Kaifeng Niu Kaifeng Niu Yicheng Shen Yicheng Shen Yicheng Shen Guannan Ma Guannan Ma Fei Chen Fei Chen Fei Chen |
author_sort |
Chengdong Xia |
title |
Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats |
title_short |
Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats |
title_full |
Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats |
title_fullStr |
Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats |
title_full_unstemmed |
Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats |
title_sort |
hepatic transcriptome analysis revealing the molecular pathogenesis of type 2 diabetes mellitus in zucker diabetic fatty rats |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2020-11-01 |
description |
Around 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat provides a successful animal model to study the pathogenesis of T2DM. Although previous hepatic transcriptome studies revealed some novel genes associated with the occurrence and development of T2DM, there still lacks the comprehensive transcriptomic analysis for the liver tissues of ZDF rats. We performed comparative transcriptome analyses between the liver tissues of ZDF rats and healthy ZCL rats and also evaluated several clinical indices. We could identify 214 and 104 differentially expressed genes (DEGs) and lncRNAs in ZDF rats, respectively. Pathway and biofunction analyses showed a synergistic effect between mRNAs and lncRNAs. By comprehensively analyzing transcriptomic data and clinical indices, we detected some typical features of T2DM in ZDF rats, such as upregulated metabolism (significant increased lipid absorption/transport/utilization, gluconeogenesis, and protein hydrolysis), increased inflammation, liver injury and increased endoplasmic reticulum (ER) stress. In addition, of the 214 DEGs, 114 were known and 100 were putative T2DM-related genes, most of which have been associated with substance metabolism (particularly degradation), inflammation, liver injury and ER stress biofunctions. Our study provides an important reference and improves understanding of molecular pathogenesis of obesity-associated T2DM. Our data can also be used to identify potential diagnostic markers and therapeutic targets, which should strengthen the prevention and treatment of T2DM. |
topic |
type 2 diabetes mellitus (T2DM) molecular pathogenesis substance metabolism inflammation liver injury ER stress |
url |
https://www.frontiersin.org/articles/10.3389/fendo.2020.565858/full |
work_keys_str_mv |
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doaj-6b91026c2d5d470dbaaef4d39ce1f9f12020-11-25T04:12:31ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-11-011110.3389/fendo.2020.565858565858Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty RatsChengdong Xia0Xiuli Zhang1Xiuli Zhang2Xiuli Zhang3Tianshu Cao4Jiannong Wang5Cuidan Li6Cuidan Li7Liya Yue8Liya Yue9Kaifeng Niu10Kaifeng Niu11Yicheng Shen12Yicheng Shen13Yicheng Shen14Guannan Ma15Guannan Ma16Fei Chen17Fei Chen18Fei Chen19Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaCAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaCAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaCAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaCAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaCAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaCAS Key Laboratory of Genome Sciences & Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaAround 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat provides a successful animal model to study the pathogenesis of T2DM. Although previous hepatic transcriptome studies revealed some novel genes associated with the occurrence and development of T2DM, there still lacks the comprehensive transcriptomic analysis for the liver tissues of ZDF rats. We performed comparative transcriptome analyses between the liver tissues of ZDF rats and healthy ZCL rats and also evaluated several clinical indices. We could identify 214 and 104 differentially expressed genes (DEGs) and lncRNAs in ZDF rats, respectively. Pathway and biofunction analyses showed a synergistic effect between mRNAs and lncRNAs. By comprehensively analyzing transcriptomic data and clinical indices, we detected some typical features of T2DM in ZDF rats, such as upregulated metabolism (significant increased lipid absorption/transport/utilization, gluconeogenesis, and protein hydrolysis), increased inflammation, liver injury and increased endoplasmic reticulum (ER) stress. In addition, of the 214 DEGs, 114 were known and 100 were putative T2DM-related genes, most of which have been associated with substance metabolism (particularly degradation), inflammation, liver injury and ER stress biofunctions. Our study provides an important reference and improves understanding of molecular pathogenesis of obesity-associated T2DM. Our data can also be used to identify potential diagnostic markers and therapeutic targets, which should strengthen the prevention and treatment of T2DM.https://www.frontiersin.org/articles/10.3389/fendo.2020.565858/fulltype 2 diabetes mellitus (T2DM)molecular pathogenesissubstance metabolisminflammationliver injuryER stress |