Significance Aerobic exercise elicits an integrated metabolic response that involves multiple tissues and confers beneficial effects to metabolic health. Here we found that this integrative response involves energy-sensing pathways in muscle and fat and circulating factors that lead to the upregulation of the type III endoribonuclease DICER in adipose tissue and the consequent increase of microRNAs. Upon upregulation, DICER and the microRNA-203-3p inhibit glucose utilization by fat cells and favor oxidative metabolism. In turn, this supports the exercised muscle with adequate substrate availability. When this pathway is disrupted, whole-body metabolism is affected, and exercise performance is impaired. Thus, adipose tissue DICER integrates signals from the exercising muscle to allow a proper metabolic response to exercise training.