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medRxiv (Medicine) 2026-06-16

Exercise Training Improves Skeletal Muscle Insulin Sensitivity and Reprograms the Adipose Transcriptome in Heavier Monozygotic Twins

Exercise training improves skeletal muscle insulin sensitivity, yet its effects on white adipose tissue remain incompletely understood. We investigated how adiposity and exercise training influence insulin-stimulated glucose uptake in skeletal muscle and abdominal subcutaneous adipose tissue (ASAT), alongside adaptations in gene expression and DNA-methylation. Ten monozygotic twin pairs discordant for BMI underwent [18F]FDG-PET/CT imaging of skeletal muscle (vastus lateralis, VL) and ASAT during a euglycemic-hyperinsulinaemic clamp before and after six months of exercise training. VL and ASAT biopsies were analyzed using mRNA-sequencing and reduced representation bisulfite sequencing. Exercise training improved whole-body and VL insulin sensitivity in leaner and heavier co-twins (p