Different obesity phenotypes correlated with the PI3K-AKT signaling pathway in tree shrews

Objective: To identify the meaningful co-expressed gene network in mRNA extracted from adipose tissue representing different obesity phenotypes in a new tree shrew model. Furthermore, to locate the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity. Methods: Ten tree shrews were selected from F1 populations and divided into 3 groups based on their Lee's index for mRNA sequencing. We identified clusters of highly correlated genes (modules) by weighted gene co-expression network analysis (WGCNA). Results: Three modules were strongly correlated with not less than one obesity phenotype (associations ranging from -0.94 to 0.85, P < 0.01). The ribosome, lysosome and ubiquitin-mediated proteolysis pathways were the most enriched pathways of the blue (including 481 genes), brown (389 genes) and turquoise (1781 genes) modules, respectively. The hub genes were determined, including UBA52 in the blue module, AKT1 in the brown module and LRRK2 in the turquoise module. Conclusions: We characterized different obesity phenotypes in tree shrews for the first time. The most represented gene AKT1 indicated the vital role of the PI3K-AKT pathway through interactions with downstream pathways and differentially expressed genes (DEGs). The work will help provide new insight into the prevention and treatment strategies of obesity. Keywords: Obesity, tree shrew (Tupaia belangeri chinensis), gene co-expression networks, PI3K/AKT pathway.