cross tissue trait-pathway network reveals the importance of oxidative stress and inflammation pathways in obesity-induced diabetes in mouse跨组织trait-pathway网络揭示氧化应激和炎症通路的重要性obesity-induced糖尿病老鼠.pdf

Cross Tissue Trait-Pathway Network Reveals the Importance of Oxidative Stress and Inflammation Pathways in Obesity-Induced Diabetes in Mouse 1,2 1 1,2 Shouguo Gao , Herbert Keith Roberts , Xujing Wang * 1 Department of Physics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 The Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract Complex disorders often involve dysfunctions in multiple tissue organs. Elucidating the communication among them is important to understanding disease pathophysiology. In this study we integrate multiple tissue gene expression and quantitative trait measurements of an obesity-induced diabetes mouse model, with databases of molecular interaction networks, to construct a cross tissue trait-pathway network. The animals belong to two strains of mice (BTBR or B6), of two obesity status (obese or lean), and at two different ages (4 weeks and 10 weeks). Only 10 week obese BTBR animals are diabetic. The expression data was first utilized to determine the state of every pathway in each tissue, which is subsequently utilized to construct a pathway co-expression network and to define trait-relevant and trait-linking pathways. Among the six tissues profiled, the adipose contains the largest number of trait-linking pathways. Among the eight traits measured, the body weight and plasma insulin level possess the most number of relevant and linking pathways. Topological analysis of the trait-pathway network revealed that the glycolysis/gluconeogenesis pathway in liver and the insulin signaling pathway in muscle are of top importance to the information flow in the network, with the high