Novel markers and networks related to restored skeletal muscle transcriptome after bariatric surgery

Objective: The aim of this study was to discover novel markers underlying the improvement of skeletal muscle metabolism after bariatric surgery. Methods: Skeletal muscle transcriptome data of lean people and people with obesity, before and 1 year after bariatric surgery, were subjected to weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Results of LASSO were confirmed in a replication cohort. Results: The expression levels of 440 genes differing between individuals with and without obesity were no longer different 1 year after surgery, indicating restoration. WGCNA clustered 116 genes with normalized expression in one major module, particularly correlating to weight loss and decreased plasma free fatty acids (FFA), 44 of which showed an obesity-related phenotype upon deletion in mice. Among the genes of the major module, 105 represented prominent markers for reduced FFA concentration, including 55 marker genes for decreased BMI in both the discovery and replication cohorts. Conclusions: Previously unknown gene networks and marker genes underlined the important role of FFA in restoring muscle gene expression after bariatric surgery and further suggest novel therapeutic targets for obesity.