Nutrient control of energy homeostasis via gut-brain neural circuits

Intestinal gluconeogenesis is a recently described function in intestinal glucose metabolism. In particular, the intestine contributes around 20-25% of total endogenous glucose production during fasting. Intestinal gluconeogenesis appears to regulate energy homeostasis via a neurally mediated mechanism linking the enterohepatic portal system with the brain. The periportal neural system is able to sense glucose produced by intestinal gluconeogenesis in the portal vein walls, which sends a signal to the brain to modulate energy and glucose homeostasis. Dietary proteins mobilize intestinal gluconeogenesis as a mandatory link between the sensing of these proteins in the portal vein and their well-known effect of satiety. Comparably, dietary soluble fibers exert their antiobesity and antidiabetic effects via the induction of intestinal gluconeogenesis. Finally, intestinal gluconeogenesis might be involved in the rapid metabolic improvements in energy homeostasis induced by gastric bypass surgeries of obesity.