Exercise training markedly augments dietary weight loss-induced improvements in multi-organ system metabolic function in people with obesity and prediabetes

The additional therapeutic effects of regular exercise during a dietary weight loss program in people with obesity and prediabetes are unclear. We evaluated the effect of 10% weight loss, induced within ~5 months by calorie-restriction alone (Diet-ONLY, n=8) or calorie-restriction plus multi-modal exercise training (Diet+EX, n=8), on metabolic function in people with obesity and prediabetes. Whole-body (primarily muscle) and hepatic insulin sensitivity were 2-3 fold greater in the Diet+EX than the Diet-ONLY group, and were accompanied by increased muscle expression of genes involved in mitochondrial biogenesis, energy metabolism and angiogenesis in the Diet+EX group without any change in the Diet-ONLY group. There were no differences between groups in plasma branched-chain amino acids or markers of inflammation, and both interventions caused similar changes in the gut microbiome. These results demonstrate that adding regular exercise to a diet-induced weight loss program has profound metabolic benefits in people with obesity and prediabetes. We obtained skeletal muscle samples from people with obesity and prediabetes before and after 10% weight loss, induced within ~5 months by calorie-restriction alone (Diet-ONLY, n=6) or calorie-restriction plus multi-modal exercise training (Diet+EX, n=7) and evaluated the effects of weight loss on skeletal muscle transcriptome by conducting RNA-seq.