When discussing how the brain regulates energy intake, we must consider “the meal” as the fundamental unit of energy intake.1
Thus, the physiological systems that exist to regulate food intake function to negatively or positively influence food intake either during a meal (within-meal) and/or between a meal, influencing the time between meals and the frequency of meal taking (inter-meal-interval).1–4
Once a meal has begun, and the ingested food enters the oral cavity, the brain perceives various components of the meal including the taste and texture of the food, potentially communicating the presence of preferred energy-rich nutrients (e.g., fats and sugars) that promote for further feeding.5–7
As food is swallowed and enters into the gastrointestinal (GI) tract, information about the volume of the ingested food through the mechanical distension of the stomach is relayed to the brain. In turn, these gastric-inhibitory signals begin to counteract the positive meal-promoting signals from the oral cavity. In addition, the various chemical and nutritive properties of the food also give rise to the release of a number of gut peptides (hormones) and neurotransmitters from the GI tract that communicate to the brain about the ongoing status of the meal. The majority of these signals are referred to as satiation signals
, or within-meal intake inhibitory signals.1
As these satiation signals accumulate, feeding rate slows and eventually satiety
, or meal termination, is achieved. Satiety then persists from the end of one meal to the start of the next meal.
To date, an extensive number of GI-derived satiation signals have been identified (some are discussed in more detail below), each with a rich literature base unto themselves. A short, non-comprehensive list of some of the classic satiation signals includes: cholecystokinin (CCK); serotonin (5-HT); peptide-YY (PYY); glutamate; enterostatin; glucagon-like-peptide-1 (GLP-1); and gastric distension. While specific receptor populations exist within the CNS for many of these GI-derived satiation signals, under normal physiological conditions, the available circulating levels of these gut-peptides and neurotransmitters are not elevated in sufficient quantity to have direct action within the brain.4, 8
Instead, the majority of GI-derived satiation signaling is communicated to the brain via afferent fibers of the vagus nerve (cranial nerve X), which innervates all of the organs within the peritoneal and thoracic cavity.4, 8, 9
Thus, the presence of food within the lumen of the GI tract results in the release of the aforementioned gut-peptides, which in turn activate specific receptors expressed on the dendritic terminals of vagal afferents that innervate the GI tract. This vagal afferent activation is then relayed to the brainstem where processing of the inhibitory signals begins. The vagal communication and CNS processing of these signals will be discussed in greater detail below.
The physiological control of meal taking is not only governed by GI-derived vagally-mediated satiation signals. The brain also detects a number of circulating hormones and nutrients (e.g., glucose, free-fatty acids) that communicate the availability of circulating and stored energy. These circulating hormones have been previously termed, “long-term energy status signals” or “adiposity signals” 2, 10
and include neuropeptides released from the pancreas (e.g., insulin, glucagon, amylin), adipose tissue (e.g., leptin, adiponectin), as well as the GI tract (e.g., ghrelin). While receptors for many of these signals exist on the vagus nerve, the principal pathway of communication for these long-term energy status signals is one of an endocrine-pathway with direct brain activation. In other words, they circulate in the blood, cross the blood brain barrier, and act directly on receptors in the brain.