Peripheral mechanisms in appetite regulation

Abstract

Peripheral mechanisms in appetite regulation include the motor functions of the stomach, such as the rate of emptying and accommodation, which convey symptoms of satiation to the brain. The rich repertoire of peripherally released peptides and hormones provides feedback from the arrival of nutrients in different regions of the gut from where they are released to exert effects on satiation, or regulate metabolism through their incretin effects. Ultimately, these peripheral factors provide input to the highly organized hypothalamic circuitry and vagal complex of nuclei to determine cessation of energy intake during meal ingestion, and the return of appetite and hunger after fasting. Understanding these mechanisms is key to the physiological control of feeding and the derangements that occur in obesity and their restoration with treatment (as shown by the effects of bariatric surgery).

Keywords: Neurohormonal; Satiation; Satiety; Stomach.

Figure 1

Integrated neurohormonal response to the ingestion of food. Sensing of different nutrients by enteroendocrine cells results in the release of diverse hormones and peptides that result in gastric accommodation to the meal, stimulation of gastric contractions that lead to emptying and, when the nutrients reach different levels of the small intestine, the release of substances that provide generally negative feedback that delays gastric emptying (e.g. CCK in the duodenum, GLP-1 and PYY in the more distal small intestine and colon).

Figure 2

Peripheral and central factors modulating appetite centers in the brain. Gastrointestinal and fat-derived hormones stimulate specific areas of the hypothalamus and brainstem that sense nutrients, and coordinate the response to hunger and the intake of food. The arcuate nucleus in the hypothalamus receives input from brainstem (e.g., vagal) nuclei as well as direct stimulation by circulating hormones through an incomplete blood brain barrier. Neurons in the arcuate nucleus are either orexigenic [e.g., contain neuropeptide Y via Y₁ receptors or agouti-related peptide (AgRP)] or anorexigenic [e.g., contain pro-opiomelanocortin (POMC)], cocaine- and amphetamine-related transcript (CART)]. POMC is a precursor of α-melanocyte stimulating hormone (α-MSH). Ultimately, other regions of the hypothalamus (the paraventricular nucleus and lateral hypothalamus) and higher centers (such as amygdala, limbic system and cerebral cortex) are stimulated to change feeding behavior by influencing the functions of the same hypothalamic nuclei. Redrawn from Camilleri M, Grudell AB. Appetite and obesity: a gastroenterologist's perspective. Neurogastroenterol Motil 2007;19:333–341.

Figure 3

The gut hormone signaling to the brain to mediate sensations of hunger and satiation. Left panel: During the fasting/preprandial state, ghrelin release from the stomach acts upon the arcuate nucleus of the hypothalamus and vagus nucleus in the brainstem to stimulate hunger. Right panel: In the postprandial state, release of anorectic hormones, PYY, GLP-1, OXM, and PP from the intestine act upon the ARC, brainstem, and vagus to cause satiation.

Figure 4

Most frequently performed operations to treat obesity (figure adapted from Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults. BMJ. 2014 Aug 27;349:g3961. doi: 10.1136/bmj.g3961).