Hormonal signaling in biology and medicine

Energy homeostasis is a finely regulated process, where food intake is the main source of energy to maintain the physiological functions of the organism and is counterbalanced by energy expenditure. When the balance between energy intake and energy expenditure fails, it triggers metabolic pathologies. Several genes have been identified to encode gut hormones involved in regulating metabolic physiology and appetite and intestinal nutrient absorption (Schwartz et al., 2000; Sahu, 2004). The endocrine activity of the intestine has been the object of intense studies for several decades, starting from the pioneering studies on secretin (Drucker et al., 2017). At the beginning of the 20th century, Bayliss and Starling by discovering this first gut hormone, secretin, in dog intestinal extract (Bayliss and Starling, 1902) founded not only gastrointestinal endocrinology but, more widely, endocrinology: in fact, in the Starling’s Croonian lecture in 1905 (Starling, 1905) the word hormone (from Greek hormoa) was coined. For many years the composition and the different functions of the factors present in the intestinal crude extract remained unclear, and only in the late 1990s the different hormones were identified. These hormones act through a strict crosstalk between intestine, where the majority of the nutrient absorption takes place, and other organs such as the brain, pancreas, liver, and heart to control food intake, intestinal absorption, and glucose homeostasis. The main gut hormones, their activities, and properties are summarized in Table 16.1. The gutebrain axis can be considered a complex neurohormonal communication network pivotal for the metabolic homeostasis. For the neural part, it consists of the central nervous system (CNS), the local enteric nervous system, the autonomous nervous system, and its associated sympathetic and parasympathetic arms; whereas in the endocrine component, it comprehends the enteroendocrine cells dispersed in the stomach and intestine. In addition, the immunological system integrated in the mucosa and the microbiota populating the gut contribute to modulate the axis activity (Bliss and Whiteside, 2018). In the axis, sensory information, nutrients, and factors produced by microbiota are converted into neural, hormonal, and immunological signals, which are relayed back and forth from the CNS to the gut and vice versa (Mayer et al., 2015). Gastric emptying is prolonged by the vagal activation and by the release of gut hormones, such as cholecystokinin (CCK), peptide YY (PYY), and glucagon-like peptide 1 (GLP-1) through a negative feedback to the brain or their local action in reducing food intake within 6 minutes of feeding in fasting re-fed rats (Davis and Smith, 1990) (Fig. 16.1).