Xin Wen1,2,3, Chunhua Qian1,2,3, Yi Zhang4, Ruijin Wu5, Liesheng Lu6, Cuiling Zhu1,2,3, Xiaoyun Cheng1,2,3, Rai Cui1,2,3, Hui You1,2,3, Fangyun Mei1,2,3, Jingyang Gao1,2,3, Feng Li1,2,3, Le Bu1,2,3, Shen Qu1,2,3. 1. Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. 2. National Metabolic Management Center, Shanghai Tenth People's Hospital, Shanghai, China. 3. Thyroid Research Center of Shanghai, Shanghai Tenth People's Hospital, China. 4. Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, National key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. 5. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. 6. Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract
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.
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.
Authors: Nicolás G Simonet; Joshua K Thackray; Berta N Vazquez; Alessandro Ianni; Maria Espinosa-Alcantud; Julia Morales-Sanfrutos; Sarah Hurtado-Bagès; Eduard Sabidó; Marcus Buschbeck; Jay Tischfield; Carolina De La Torre; Manel Esteller; Thomas Braun; Mireia Olivella; Lourdes Serrano; Alejandro Vaquero Journal: Sci Adv Date: 2020-07-24 Impact factor: 14.136