Despite being recognized as a key element in the etiology of type 2 diabetes, skeletal muscle insulin resistance lacks a unifying mechanism that can be consistently translated to human disease or pathobiology. Moreover, whether improvements in insulin sensitivity with weight loss and exercise share common underpinnings is unclear. In this context, bariatric surgery–induced weight loss, with or without concomitant exercise training, provides a conceptual and practical framework to examine important questions about treatment for insulin resistance. We recently reported that insulin resistance is not generally normalized in the weeks to months after RYGB surgery and that regular exercise can further improve peripheral insulin sensitivity.^[4] In the present study, we examined whether alterations in mitochondrial energetics or intramyocellular lipids correspond with improved insulin sensitivity following RYGB surgery with or without regular exercise.