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

Author:

Ouni Meriem12ORCID,Kovac Leona12,Gancheva Sofiya234,Jähnert Markus12,Zuljan Erika12,Gottmann Pascal12,Kahl Sabine23,de Angelis Martin Hrabĕ256,Roden Michael234,Schürmann Annette127

Affiliation:

1. German Institute of Human Nutrition Department of Experimental Diabetology Potsdam Germany

2. German Center for Diabetes Research (DZD) Munich Germany

3. Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Heinrich Heine University Düsseldorf Germany

4. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research Heinrich Heine University Düsseldorf Germany

5. Institute of Experimental Genetics, German Mouse Clinic Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg Germany

6. School of Life Sciences Technical University Munich Freising Germany

7. Institute of Nutritional Sciences University of Potsdam Nuthetal Germany

Abstract

AbstractObjectiveThe aim of this study was to discover novel markers underlying the improvement of skeletal muscle metabolism after bariatric surgery.MethodsSkeletal 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.ResultsThe 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.ConclusionsPreviously 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.

Funder

Deutsche Forschungsgemeinschaft

Schmutzler Stiftung

Deutsche Diabetes Gesellschaft

Publisher

Wiley

Subject

Nutrition and Dietetics,Endocrinology,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)

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