The sensing and signaling of ingested nutrients in the gastrointestinal (GI) tract is crucial for regulating energy homeostasis. The GI tract activates neural and endocrine pathways that connect with other signals, such as fat energy storage and utilization. Short-term regulation of food intake, like individual meal size and duration, is influenced by satiety signals from the GI tract. The luminal contents trigger vagal afferent pathways, which suppress meal size. Additionally, various GI hormones released by nutrients affect food intake. Cholecystokinin (CCK) is a well-known satiety hormone that decreases food intake after exogenous administration. Other GI hormones in this class include glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). Both lean and obese humans experience decreased food intake upon injection of exogenous PYY. Exendin-4, a long-acting analogue of GLP-1, is currently used for weight control in humans.

When the meal enters the small intestine, it regulates the rate of gastric emptying through neural and hormonal pathways. Afferent neurons, mostly of vagal origin, respond to nutrients, [H+], and the hyperosmotic content of chyme as it enters the duodenum. This triggers reflex activation of vagal efferent outflow, which reduces antral contractions, contracts the pylorus, and decreases proximal gastric motility, leading to inhibition of gastric emptying. This pathway also inhibits gastric acid secretion when nutrients are present in the duodenal lumen. Cholecystokinin (CCK) is released by endocrine cells in the duodenal mucosa in response to nutrients, playing a physiological role in regulating gastric emptying, gallbladder contraction, sphincter of Oddi relaxation, and pancreatic secretion. Recent evidence suggests that CCK acts both directly (inhibiting gastric emptying) and indirectly (stimulating vagal afferent fiber discharge to produce an indirect vagovagal reflex-mediated decrease in gastric emptying).

Despite these inhibitory pathways, gastric emptying can still occur. As chyme moves further down the small intestine into the jejunum, the amount of chyme in the duodenum decreases. Consequently, the strength of intestinal feedback inhibition weakens as duodenal sensory mechanisms receive less activation from nutrients. This leads to an increase in intragastric pressure in the proximal portion of the stomach, pushing material into the antrum and towards the antral pump. Antral peristaltic contractions intensify, resulting in the opening of the pylorus and the release of gastric contents into the duodenum.
Thegastrointestinal(GI)tractplaysamajorroleinthesensingandsignalingofingestednutrientsbyactivatingneuralandendocrinepathwaysthatconnectwithothersignals,suchasfatenergystorageandutilization,whichtogetherregulateenergyhomeostasis.SatietysignalsfromtheGItractaregenerallyinvolvedinshort-termregulationoffoodintake,suchasindividualmealsizeandmealduration.Forexample,theluminalcontentsactivatevagalafferentpathways,leadingtosuppressionofmealsize.Inaddition,severalGIhormonesreleasedbynutrientsalsoinfluencefoodintake.Cholecystokinin(CCK)isawell-describedsatietyhormone;itisreleasedbynutrientsanddecreasesfoodintakeafterexogenousadministration.OtherGIhormonesinthisclassincludeglucagon-likepeptide1(GLP-1)andpeptideYY(PYY).Inbothleanandobesehumans,injectionofexogenousPYYinhibitsfoodintake.Along-actinganalogueofGLP-1,exendin-4,iscurrentlybeingusedasanagentforweightcontrolinhumans.
antral pump), opening of the pylorus to allow the contents to pass, and simultaneous inhibition of duodenal segmental contractions. Liquids and the semiliquid chyme flow down the pressure gradient from the stomach to the duodenum.
As the meal enters the small intestine, it feeds back via both neural and hormonal pathways to regulate the rate of gastric emptying based on the chemical and physical composition of the chyme. Afferent neurons, predominantly of vagal origin, respond to nutrients, [H+], and the hyperosmotic content of chyme as it enters the duodenum. Reflex activation of vagal efferent outflow decreases the strength of antral contractions, contracts the pylorus, and decreases proximal gastric motility (with a decrease in intragastric pressure), thereby resulting in inhibition (slowing) of gastric emptying. This same pathway is responsible for the inhibition of gastric acid secretion that occurs when nutrients are in the duodenal lumen. Cholecystokinin (CCK) is released from endocrine cells in the duodenal mucosa in response to such nutrients. This hormone is physiologically important, in addition to its role in neural pathways, in the regulation of gastric emptying, gallbladder contraction, relaxation of the sphincter of Oddi, and pancreatic secretion. Recent evidence suggests that CCK acts both directly (inhibits gastric emptying) and indirectly (stimulates vagal afferent fiber discharge to produce an indirect vagovagal reflex–mediated decrease in gastric emptying).
How then can gastric emptying proceed in the face of these inhibitory pathways? The amount of chyme in the duodenum decreases as it passes further down the small intestine into the jejunum; thus the strength of intestinal feedback inhibition fades as there is less activation of duodenal sensory mechanisms by nutrients. At this time, intragastric pressure in the proximal portion of the stomach increases, thereby moving material into the antrum and toward the antral pump. Antral peristaltic contractions again deepen and culminate in opening of the pylorus and release of gastric contents into the duodenum.