Cellular mechanism of diabetes remission by bariatric surgery

Bariatric surgery is a powerful therapy for type 2 diabetes in patients with obesity. The mechanism of insulin sensitization by surgery has been extensively investi-gated in weight loss-dependent and weight loss-independent conditions. How-ever, a consensus remains to be established regarding the underlying mechanisms. Energy deficit induced by calorie restriction (CR), that occurs both before and after surgery, represents a unique physiological basis for insulin sensi-tization regardless of weight loss. In support, we integrate evidence in the litera-ture to provide an energy-based view of insulin sensitization as follows: surgery improves insulin sensitivity through the energy deficit induced by CR, leading to correction of mitochondrial overload in multiple cell types; this then triggers func-tional reprogramming of relevant tissues leading to diabetes remission.