Regulation of nutrient metabolism and energy expenditure

The requisites for energy expenditure are covered mainly by two major substrates, glucose and free fatty acids (FFA). Their regulation and metabolism differ. After carbohydrate ingestion, glucose is rapidly oxidized or stored in muscles and liver. There is a constant alternance between glucose storage as glycogen after meals and glycogen mobilization in the postabsorptive state when plasma glucose has returned to the basal state. Impairment of this alternance, in particular when glycogen stores are not being used, may lead to glucose intolerance and insulin resistance. Ingestion of lipids is not followed by an immediate increase in lipid oxidation, but FFA are stored as triglycerides in different tissues. Lipolysis occurs in the fasting state from tissue triglycerides and favors lipid oxidation. Lipid oxidation is typically increased in obesity. The preferential use of FFA from triglyceride stores for energy expenditure in obesity is responsible for the decrease in glucose mobilization from glycogen stores. This leads to a negative feedback of muscle and liver glycogen on glycogen synthase activity and consequently on glucose storage. It results in glucose intolerance after carbohydrate ingestion. Diabetes develops in obesity, usually after a long period of glucose intolerance, when glycemia does not return to the basal state. In obesity, glucose intolerance and insulin resistance can be prevented, or if already existing, can be decreased by stimulating glycogen mobilization by exercise, thermogenesis-stimulating drugs, and weight loss, which reduces fat stores and decreases lipid oxidation.