(A) Basal plasma endotrophin concentrations in lean-IS (n = 10), obese-IS (n = 10) and obese-IR (n = 10), groups. *P < 0.05 versus lean-IS and †P < 0.05 versus obese-IS, by Tukey’s honest significant difference (HSD) test. (B–D) Serial plasma endotrophin (B), glucose (C), and insulin (D) concentrations assessed over 24 hours with meals provided at 0 (0700 hours), 6 (1300 hours), and 12 (1900 hours) hours in a subset of participants in the obese-IS (n = 4; black) and obese-IR (n = 4; orange) groups. (E) Plasma endotrophin concentrations before and after approximately 18% weight loss in people with obesity and type 2 diabetes (n = 15). *P < 0.05 versus before, by 2-tailed Students t test for paired samples. (F) Glucose uptake in myotubes treated with and without insulin, apigenin (an inhibitor of glucose uptake), endotrophin, and/or a neutralizing anti-endotrophin monoclonal antibody. Conditions with different symbols are significantly different (P < 0.01) from each other by Games-Howell test. Data are the mean ± SEM. Individual values are shown as open circles in A, E, and F.