Integrated Upper Gastrointestinal Response to Food Intake Michael Camilleri  Gastroenterology  Volume 131, Issue 2, Pages 640-658 (August 2006) DOI: 10.1053/j.gastro.2006.03.023 Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 1 Upper gastrointestinal manometric tracing in a healthy volunteer showing an interdigestive MMC during fasting (left) and irregular high-amplitude and sustained contractile activity in the stomach, duodenum, and proximal jejunum during the postprandial period (right). Reprinted with permission.3 Gastroenterology 2006 131, 640-658DOI: (10.1053/j.gastro.2006.03.023) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 2 (A) The gastric accommodation response to the ingestion of a meal. In the top tracing, gastric volume response is measured with an intragastric balloon, in which the air has been clamped at constant pressure by means of a barostat. At the lower left, the gastric transaxial images acquired by single photon emission computed tomography are reconstructed in the fasting and postprandial (PP) periods. At the lower right, the average fasting and postprandial volumes of the entire, proximal, and distal stomach in a group of 73 healthy volunteers are plotted. Adapted and reprinted with permission.4–6 (B) Time course of gastric emptying of solids and volume response to feeding in healthy humans. Note that the volume response is demonstrable almost immediately after the meal and that there is a gradual reduction in volume such that by 3 hours after meal ingestion, it is estimated that the calculated volume of meal in the stomach approximates the measured gastric volume. Reprinted with permission.28 Gastroenterology 2006 131, 640-658DOI: (10.1053/j.gastro.2006.03.023) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 3 Gastrin stimulates acid secretion primarily through activation of CCK2 receptors on ECL cells through release of histamine. CCK counterbalances gastrin action through release of somatostatin (SST) from antral or fundic D cells, which inhibit histamine release from ECL cells as well as gastrin release from G cells. Despite its nanomolar affinity for CCK2 receptors on cells representing the positive effector pathway, the net effect of CCK on acid secretion is inhibitory. Functional inactivation of both gastrin and CCK results in normal acid secretion following pylorus ligation, whereas gastrin deficiency alone is characterized by hypochlorhydria. Reprinted with permission.51 Gastroenterology 2006 131, 640-658DOI: (10.1053/j.gastro.2006.03.023) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 4 Emulsification, hydrolysis, and micelle formation in the absorption of fat. Bile salts have both hydrophilic and hydrophobic domains; on exposure to triglyceride, the hydrophobic portions of bile salts intercalate into the lipid, with the hydrophilic domains remaining at the surface. Coating with bile salts aids in breakdown of large aggregates or droplets into smaller droplets, which present a larger surface area for the action of pancreatic lipase to hydrolyze triglyceride into a 2-monoglyceride and free fatty acids. Meanwhile, the monoglycerides and fatty acids retain their association with bile salts and complex with other lipids to form structures called micelles, small aggregates of mixed lipids and bile salts suspended within chyme. As the ingesta is mixed, micelles are brought into contact with the brush border and the lipids, including monoglyceride and fatty acids, are absorbed. Bile salt micelles (or vesicles) overcome the diffusion barrier resistance provided by the unstirred water layer. In the absence of bile acids, individual lipid molecules must diffuse across the barriers overlying the microvillus border of the intestinal epithelial cells (thin arrow). Hence, uptake of these molecules is largely diffusion limited. In the presence of bile acids (wide arrow), large amounts of these lipid molecules are delivered directly to the aqueous-membrane interface so that the rate of uptake is greatly enhanced. Adapted and reprinted with permission.90 Gastroenterology 2006 131, 640-658DOI: (10.1053/j.gastro.2006.03.023) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 5 Interactions among hormonal and neural pathways that regulate food intake and body fat mass. Dashed lines indicate hormonal inhibitory effects, and solid lines indicate stimulatory effects. The paraventricular and arcuate nuclei each contain neurons that are capable of stimulating or inhibiting food intake. Y1R and Y2R, Y1 and Y2 subtypes of the NPY receptor; MC4R, melanocortin 4 receptor; GHsR, growth hormone secretagogue receptor; AgRP, agouti-related protein; POMC, proopiomelanocortin; α-MSH; α–melanocyte-stimulating hormone; LEPR, leptin receptor; INSR, insulin receptor. Reprinted with permission.138 Gastroenterology 2006 131, 640-658DOI: (10.1053/j.gastro.2006.03.023) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions