scholarly journals Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Siyi Zhang ◽  
Bo Wang ◽  
Jingsong Shi ◽  
Jing Li

The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

2005 ◽  
Vol 34 (2) ◽  
pp. 299-315 ◽  
Author(s):  
Young Ho Suh ◽  
Younyoung Kim ◽  
Jeong Hyun Bang ◽  
Kyoung Suk Choi ◽  
June Woo Lee ◽  
...  

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.


2008 ◽  
Vol 67 (4) ◽  
pp. 395-403 ◽  
Author(s):  
Melissa J. Morine ◽  
Cathal O'Brien ◽  
Helen M. Roche

The Human Genome Project and rapid advances in high-throughput molecular technologies are providing an unprecedented opportunity to advance the understanding of the common polygenic diet-related diseases, including obesity, the metabolic syndrome, type 2 diabetes mellitus, CVD and some cancers. In particular, transcriptomic approaches that allow multiple simultaneous gene-expression profiles facilitate the characterisation of metabolic perturbations that underlie diet-related pathologies. The present paper will focus on ‘transcriptomic signatures’ to characterise and understand the molecular mechanisms that accurately reflect ‘metabolic health’.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Wen-Yu Cheng ◽  
Huai-Jie Jia ◽  
Xiao-Bing He ◽  
Guo-Hua Chen ◽  
Yuan Feng ◽  
...  

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirusrelationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirusinteraction.


Author(s):  
Chunhong LI ◽  
Qingqing NONG ◽  
Bin GUAN ◽  
Haoyu HE ◽  
Zhiyong ZHANG

Background: We attempt to identify specific differentially methylated and expressed genes in people with longevity family history, it will contribute to discover significant features about human longevity. Methods: A prevalence study was conducted during October 2017 to January 2019 in Bama County of Guangxi, China and individuals were recruited and grouped into longevity family (n=60) and non-longevity family (n=60) to identify differentially methylated genes (DMGs). The expression profile dataset GSE16717 was downloaded from the GEO database in which individuals were divided into 3 groups, namely longevity (n=50), longevity offspring (n=50) and control (n=50) for identifying differentially expressed genes (DEGs). It was considered significantly different when P or adjusted P0.05. Results: In total, 117 longevity-related hypermethylated genes enriched in interleukin secretion/production regulation, chemokine signaling pathway and natural killer cell-mediated cytotoxicity. Another 296 significant key longevity-related DEGs primarily involved in protein binding, nucleus, cytoplasm, T cell receptor signaling pathway and Metabolic pathway, H19 and PFKFB4 were found to be both methylated and downregulated in people with longevity family history. Conclusion: Human longevity-specific genes involve in many immunity regulations and cellular immunity pathways, H19 and PFKFB4 show hypermethylated and suppressed status in people with longevity family history and might serve as longevity candidate genes.


2022 ◽  
Author(s):  
Lyubov N. Chuvakova ◽  
Sergey Yu. Funikov ◽  
Artem I. Davletshin ◽  
Irina B. Fedotova ◽  
Mikhail B. Evgen'ev ◽  
...  

Audiogenic epilepsy (AE), developing in rodent strains in response to sound, is widely used as the model of generalized convulsive epilepsy, while the molecular mechanisms determining AE are currently poorly understood. The brain region that is crucial for AE development isthe inferior and superior colliculi (IC, SC). We compared IC-SC gene expression profiles in rats with different AE susceptibility using transcriptome analysis.The transcriptomes were obtained from the IC-SC of Wistar rats (with no AE), Krushinsky-Molodkina (KM) strain rats (100% AE susceptible), and ”0” strain rats (with no AE) selected from F2 KM x Wistar hybrids for AE absence. KM gene expression displayed characteristic differences inboth of the strains that were not susceptible to AE. There was increased expression of a number of genes responsible for positive regulation of the MAPK signaling cascade, as well as of genes responsible for the production of interferon and several other cytokines. An increase in the expression levels of theTTR gene was found in KM rats, as well as significantly lower expression of the Msh3 gene (involved in post-replicative DNA repair systems). AE was also describedin the 101/HY mouse strain with a mutation in the locus controlling DNA repair. The DNA repair system defects could be the primary factor leading to the accumulation of mutations, which, in turn, promote AE. Keywords: udiogenic seizure, KM strain, transcriptome, TTR gene, Msh3 gene, DNA repair


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xu Zhang ◽  
Feng Huang ◽  
Diyuan Yang ◽  
Tao Peng ◽  
Gen Lu

Respiratory syncytial virus (RSV) is the most common respiratory virus and is associated with pediatric pneumonia, causing bronchiolitis and significant mortality in infants and young children. MicroRNAs (miRNAs) are endogenous noncoding small RNAs that function in gene regulation and are associated with host immune response and disease progression. In the present study, we profiled the global transcriptome and miRNAome of whole blood samples from children with mild or severe RSV-associated pneumonia, aiming to identify the potential biomarkers and investigate the molecular mechanisms of severe RSV-associated pediatric pneumonia. We found that expression profiles of whole blood microRNAs and mRNAs were altered and distinctly different in children with severe RSV-associated pneumonia. In particular, the four most significantly upregulated miRNAs in children with severe RSV-associated pneumonia were hsa-miR-1271-5p, hsa-miR-10a-3p, hsa-miR-125b-5p, and hsa-miR-30b-3p. The severe RSV-associated pneumonia-specific differentially expressed miRNA target interaction network was also contrasted. These target genes were further analyzed with Gene Ontology enrichment analysis. We found that most of the target genes were involved in inflammatory and immune responses, including the NF-κB signaling pathway, the MAPK signaling pathway, and T cell receptor signaling. Our findings will contribute to the identification of biomarkers and new drug design strategies to treat severe RSV-associated pediatric pneumonia.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Bai ◽  
Wenwen Yang ◽  
Yao Lu ◽  
Wei Wei ◽  
Zongbao Li ◽  
...  

This study is to identify the circular RNA (circRNA) expression profile that is functionally related to pancreatic islet β-cell autophagy and their potential regulation mechanisms in type 2 diabetes mellitus (T2DM). T2DM rat model was constructed by administration of high-fat and high-sugar diet. β-cells were isolated from islets by flow cytometry. CircRNA expression profile in β-cells was detected by circRNA microarrays, and the differentially expressed circRNAs were identified and validated by qRT-PCR. MicroRNA (miRNA) target prediction software and multiple bioinformatic approaches were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. A total of 825 differentially expressed circular transcripts were identified in T2DM rats compared with control rats, among which 388 were upregulated and 437 were downregulated. Ten circRNAs were identified to have significant differences by qRT-PCR. GO analysis enriched terms such as organelle membrane and protein binding and the top enriched pathways for the circRNAs included MAPK signaling pathway. The differentially expressed circRNAs might involve in MAPK signaling pathway, apoptosis, and Ras signaling pathway. We speculate that these circRNAs, especially rno_circRNA_008565, can regulate the autophagy of islet β-cells via interactions with miRNA. Dysregulation of several circRNAs may play a role in T2DM development, and rno_circRNA_008565 may be a potential regulator of β-cell autophagy.


2018 ◽  
Vol 140 (2) ◽  
pp. 87-96
Author(s):  
Haitao Xu ◽  
Fusheng Yao

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is rare but a clinicopathologically distinct B-cell malignancy. This study assessed differentially expressed genes (DEGs) to identify potential WM biomarkers and uncover the underlying the molecular mechanisms of WM progression using gene expression profiles from the Gene Expression Omnibus database. DEGs were identified using the LIMMA package and their potential functions were then analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and the protein-protein interaction (PPI) network analysis by using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs were enriched in different GO terms and pathways, including the apoptotic process, cell cycle arrest, immune response, cell adhesion, mitogen-activated protein kinase signaling pathway, toll-like receptor signaling pathway, and the gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis of the GSE9656 dataset identified 7 hub genes that might play an important role in WM development and progression. Some of the candidate genes and pathways may serve as promising therapeutic targets for WM.


Sign in / Sign up

Export Citation Format

Share Document