The role of the gastrointestinal tract in the control of energy balance

The gastrointestinal tract (GIT) is part of a major physiological system involved in the regulation of the body's energy homeostasis. GIT secretes several peptides that influence energy balance through regulation of food intake, energy expenditure and metabolism, besides their local effects controlling gastric-empting, gut motility and nutrient utilization. These peptides integrate a two-way communication axis with the central nervous system, particularly involving the arcuate nucleus (ARC) of the hypothalamus and the nucleus of the solitary tract (NTS). As their primary role, GIT-derived peptides act as "satiety signals" to the brain, modulating various physiological events related to the meals and the inter-meals periods. Since the pioneering studies with cholecystokinin (CCK) four decades ago, many other peptides, receptors and intracellular pathways have been revealed, mostly promoting reduction of food intake. The discovery of ghrelin in 1999 unveiled a new paradigm in this system, presenting the first and the only peripheral hormone with orexigenic properties to date. In the last years, a new player has entered into the game with the demonstration that intestinal microbiota is linked to obesity and metabolic disorders. In view of the alarming incidence of obesity, diabetes and metabolic syndrome (MS) worldwide, our understanding on how this communication axis between GIT and brain operates is critical for the development of efficient and safe therapies to fight against these major threats of human health.