Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity‐related diabetes

• Published in: Journal of cellular biochemistry Vol. 120; no. 4; pp. 6763 - 6771
• Main Authors: Wen, Xin, Qian, Chunhua, Zhang, Yi, Wu, Ruijin, Lu, Liesheng, Zhu, Cuiling, Cheng, Xiaoyun, Cui, Rai, You, Hui, Mei, Fangyun, Gao, Jingyang, Li, Feng, Bu, Le, Qu, Shen
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2019
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Biological activity; Diabetes; Diabetes mellitus; DNA microarrays; Encyclopedias; Functional analysis; Gastric mucosa; Gene expression; gene microarray; Genes; Genomes; Lymphocytes; Lymphocytes T; Obesity; Patients; Polymerase chain reaction; Proteins; Stomach; type 2 diabetes mellitus (T2DM); gastric mucosa; gene microarray; obesity; type 2 diabetes mellitus (T2DM)
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.27976

Background and Objective The stomach plays an important role in obesity and obesity‐related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes. Methods We performed gene microarray and real time‐polymerase chain reaction (RT‐PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes. Results In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co‐regulated in both comparisons. Seven differentially expressed genes were validated by RT‐PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G‐protein coupled receptor biological processes, and primarily participated in the PI3K‐Akt and AGE‐RAGE signaling pathways. Conclusions Obesity and obesity‐related diabetes are associated with important gene expression and pathway alterations in the stomach. 1. Systematically examined obesity‐related changes at the transcriptional level in the stomach. 2. The validated genes (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, ASIC3) may provide potential therapeutic targets for obesity and related diseases. 3. The effects of genes expressed in gastric mucosa mainly influence metabolic, T cell and G‐protein coupled receptor biological processes, PI3K‐Akt and AGE‐RAGE signaling pathways.