WGCNA analysis of the subcutaneous fat transcriptome in a novel tree shrew model.

Obesity involves genetic and environmental factors. The co-expression gene network in relevant tissues in different obesity groups provides an entrance for profiling and identifying associated pathways and genes. We aim to identify the meaningful co-expressed gene network in mRNA extracted from adipose tissues representing different obesity phenotypes in a new tree shrew model. Furthermore, to find the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity. Ten tree shrews were selected from F1 populations and divided into three groups based on their Lee's index for mRNA sequencing. We identified clusters of highly correlated genes (modules) in differently expressed genes by weighted gene co-expression network analysis. Three modules were firmly correlated with not less than one obesity phenotype (associations ranging from -0.94 to 0.85, P < 0.01). The genes from the blue module (including 481 genes) are mostly enriched in the ribosome pathway. The genes from the brown module (including 389 genes) are mostly enriched in the lysosome pathway. The genes from the turquoise module (including 1781 genes) are mostly enriched in the ubiquitin-mediated proteolysis pathway. The hub gene in each module was determined, including UBA52 in the blue module, AKT1 in the brown module, and LRRK2 in the turquoise module. After profiling and analyzing the co-expression gene network of obese tree shrew, we identified differently expressed genes and pathways (ribosome, lysosome and ubiquitin-mediated proteolysis pathway) that might be involved in the development of obesity. Further study of the differently expressed genes and pathways might provide new targets for the prevention and therapy of obesity. Impact statement We constructed the transcriptomic network in adipose tissue in lean, moderate obesity and severe obesity groups of tree shrew for the first time. Compared to other laboratory animal models, the tree shrew is a prospective laboratory animal that has a closer genetic association with primates than with rodents. It is widely used in biomedical researches. Enrichment analyses revealed several molecular biological processes were involved in the ribosome, lysosome, and ubiquitin-mediated proteolysis process. These results provided insights into new targets for the prevention and therapy of obesity and a novel research model for obesity.