To examine factors underlying why most, but not all, adults with obesity exhibit impaired insulin‐mediated glucose uptake, we compared: (1) adipose tissue fatty acid (FA) release, (2) skeletal muscle lipid droplet (LD) characteristics, and (3) insulin signalling events, in skeletal muscle of adults with obesity with relatively high versus low insulin‐mediated glucose uptake. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.