摘要:SummarySlow oxidative muscle, most notably the soleus, is inherently well equipped with the molecular machinery for regulating blood-borne substrates. However, the entire human musculature accounts for only ∼15% of the body’s oxidative metabolism of glucose at the resting energy expenditure, despite being the body’s largest lean tissue mass. We found the human soleus muscle could raise local oxidative metabolism to high levels for hours without fatigue, during a type of soleus-dominant activity while sitting, even in unfit volunteers. Muscle biopsies revealed there was minimal glycogen use. Magnifying the otherwise negligible local energy expenditure with isolated contractions improved systemic VLDL-triglyceride and glucose homeostasis by a large magnitude, e.g., 52% less postprandial glucose excursion (∼50 mg/dL less between ∼1 and 2 h) with 60% less hyperinsulinemia. Targeting a small oxidative muscle mass (∼1% body mass) with local contractile activity is a potent method for improving systemic metabolic regulation while prolonging the benefits of oxidative metabolism.Graphical abstractDisplay OmittedHighlights•We developed a method to capitalize upon the unique phenotype of the soleus•“A high quality versus large quantity perspective” for muscle activation•Singular movement targeting the 1 kg soleus easily sustains oxidative metabolism•This method provides adistinctmuscular activity stimulus for metabolic controlHealth sciences; Physiology; Human metabolism.