Role of the Gut in the Regulation of Energy Balance and Energy Stores

The gut is responsible for food intake, which, together with energy expenditure, determines the status of energy balance. Positive net caloric intake directly correlates with the size of fat tissue weight gain. The gut fulfills the function of regulating food intake by communicating with other organ systems, particularly the brain, to control meal content, frequency, and size. While it receives efferent output from the brain to signal hunger, satiation, or general “appetite” based on the body’s metabolic and hedonic needs, it sends afferent signals to inform the brain the status of food intake, completing a negative feedback loop. Broadly speaking, the gut has “taste receptors” throughout the intestine, in addition to the traditional taste buds in the mouth. While the bolus of food ingested is sensed by mechanosensors in the gut, the nutrients derived from ingested foods are sensed by chemosensors, which leads to the secretion of many peptide hormones by the enteroendocrine cells. These gut hormones may communicate with the brain directly via endocrine action, or indirectly through vagal afferent neurons, to exert their orexigenic or anorexigenic effects. This chapter summarizes major gut hormones related to energy metabolism, their roles in regulating appetite and food intake, and where evidence calls for, their roles in long-term energy balance, usually in concert with signals from adipose tissue and with nonhomeostatic signals. The roles of bile acids and gut microbiota and their interplays with the gut hormones and other organ systems involved in energy metabolism are also briefly discussed.