TY - JOUR A1 - Gancheva, Sofiya A1 - Ouni, Meriem A1 - Jelenik, Tomas A1 - Koliaki, Chrysi A1 - Szendroedi, Julia A1 - Toledo, Frederico G. S. A1 - Markgraf, Daniel Frank A1 - Pesta, Dominik H. A1 - Mastrototaro, Lucia A1 - De Filippo, Elisabetta A1 - Herder, Christian A1 - Jähnert, Markus A1 - Weiss, Jürgen A1 - Strassburger, Klaus A1 - Schlensak, Matthias A1 - Schürmann, Annette A1 - Roden, Michael T1 - Dynamic changes of muscle insulin sensitivity after metabolic surgery JF - Nature Communications N2 - The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-12081-0 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER -