Chyme is likely to reach the jejunum before the end of the meal, and the distension which results may play a part in the initiation and maintenance of satiety. The effects of digesta reaching the duodenum and jejunum could be mediated by stretch receptors, osmoreceptors or chemoreceptors. Although there is adequate neurophysiological evidence for receptors sensitive to several chemical types, that for osmoreceptors is weak. However, there is much circumstantial evidence that they are important in the control of food intake.
In later chapters, the role of learned associations between the sensory properties of foods and the consequences of eating those foods will be emphasized. Most research with simple-stomached animals has been carried out with hormones and metabolites, but Bardos (2001) demonstrated aversion in rats to a food taste that had been paired with mechanical stimuli (balloon distension) applied in both small and large intestinal loops. Distension of the intestines is not simply, therefore, the affector of a primary negative feedback, it also contributes to the secondary, learned feedback complex, which is now viewed as being of the utmost importance in the control of food intake and choice.
Feedbacks from the Gastrointestinal Tract 63
Poultry
Duodenal infusion of glucose solutions inhibits feeding but potassium chloride and sorbitol solutions, which are not absorbed, have a more prolonged effect (see below) suggesting that it is the physical presence rather than the chemical nature that is important.
Distension of the cloaca or rectum results in reduced food intake, so that it seems reasonable to conclude that stimulation of stretch receptors at any point along the digestive tract will result in hypophagia, and that this distension during and after meals is a factor in the control of meal size and frequency.
Some of the solutions injected into the crop (Shurlock and Forbes, 1981b) probably found their way further along the digestive tract and might have affected food intake by means of gastric or intestinal stimulation. This was investigated by slowly injecting 10 ml of 3 osm solutions of glucose, sorbitol or potassium chloride into the duodenum of cockerels through permanently implanted cannulae. Compared with control (no injection), water had no effect on intake, nor did glucose, while sorbitol and potassium chloride caused highly significant decreases in intake. Neither did intra-duodenal glucose infusions affect food intake in the work of Lacey et al. (1986). Glucose is absorbed quickly from the small intestine and would not be present for long enough to result in prolonged stimulation of gut distension or of osmoreceptors, while the non-absorbed solutes would continue to stimulate these receptors, resulting in depressed voluntary intake. In birds that had been fasted overnight before these same treatments were given, glucose injection into the duodenum did significantly depress feeding, perhaps because the liver content of glycogen was depleted so that it took up glucose, which stimulated liver receptors (see Chapter 4).
Vagotomy at the level of the proventriculus prevented the effects of glucose solutions infused into the duodenum of chickens (Shaobi and Forbes, 1987) but, as the nerve section included fibres to and from the liver and pancreas as well as the duodenum, it is not completely clear whether the glucose was acting primarily on the duodenum or elsewhere. It seems likely that osmoreception is important in birds, although it is possible that the effects of hypertonic solutions are due to physical distension of the duodenum by the increase in volume as water is drawn from the blood. It is also worth noting that hypertonic solutions stimulate gut motility, this being likely to stimulate mechanoreceptors in the gut wall.
Pigs
Food intake by hungry growing pigs is reduced by injection of 250 ml of a 150 g/l solution of glucose into the duodenum. When the treatment was given 3 min after food had been offered following an overnight fast, intake was 445 g compared with 782 g for control, whereas 250 ml of a 15% solution of neutral fat or a 10% solution of amino acids had no effect (Stephens, 1980). This suggests that there are specific glucose receptors in the duodenum rather than
osmo- or distension receptors. The effect of 250 ml of a 150 g/l glucose solution into the duodenum was prevented by prior bilateral thoracic vagotomy (Stephens, 1985), confirming that there is a neural link with the CNS rather than a humoral one in this context.
2-deoxy-D-glucose (2DG, a glucose antimetabolite) did not affect feeding when given just after the start of the meal, but it did block the effect of glucose, suggesting that some of the hypophagic effect of glucose solutions infused into the duodenum is not osmotic unless, of course, the glucose has to be absorbed before gaining access to the osmoreceptors.
Duodenal infusions of solutions of non-absorbable sugars such as mannitol have a more prolonged action than glucose, presumably due to the osmotic drawing of water into the intestinal lumen, which causes greater stretch of mechanoreceptors. Infusion of a fat emulsion also depressed intake, but this was blocked by local anaesthetic as was the effect of glucose given into the duodenum. A large increase in the osmolality of duodenal contents occurs during a normal large meal, so that these receptors could be of physiological importance in the termination of meals (Houpt, 1983). Xylose solutions, which are not absorbed, are less effective than glucose or sodium chloride when given into the duodenum, which suggests that the osmoreceptors are not on the surface of cells exposed directly to the infusate. Most of these effects can be blocked by a local anaesthetic given in the infusion, so the receptors are not thought to be deeper than the mucosal layer.
Houpt (1983) suggested that good control over food intake in the pig could be exerted by a combination of three factors working largely in the duodenum: (i) osmotic sensitivity, which is precise but not directly related to nutritive value; (ii) CCK (cholecystokinin) responses to protein and fat in duodenal digesta; and (iii) glucoreceptors in the intestine. The satiating effect of glucose infused into the duodenum of young pigs has been apportioned as follows: 20% due to fluid movements from blood to gut, 55% is osmotic within the gut, while the remaining 25% is hormonal, perhaps involving CCK.
Despite the emphasis on osmolality as a major factor in intake control in pigs, with normal feeding and free access to drinking water, osmolality of duodenal fluid never exceeded 300 mosmol/kg. It is uncertain, therefore, whether osmolality normally plays a significant part in the control of feeding.
Protein infused into the stomach or protein hydrolysate into stomach, duodenum, jejunum or ileum all decrease intake approximately in proportion to the amount of energy infused. Glucose infusion into the duodenum slowed gastric emptying so that the total flow of energy through the duodenum was unchanged, but the mechanisms for this apparent control of energy flow are not understood. Infusion of fat into the stomach or duodenum, or fat, bile salts and lipase into the upper jejunum, depressed intake in pigs (Rayner and Gregory, 1989). Fat, bile and lipase infusions into the ileum had no effect on that meal but did tend to reduce the size of the next meal. Older pigs, > 60 kg body weight, still respond to glucose and fatty acid infusions, so their
‘overeating’ is not due to lack of sensitivity to nutrients in the gastrointestinal tract.
Feedbacks from the Gastrointestinal Tract 65
Ruminants
There are tension receptors with vagal afferent fibres in the duodenum of the sheep that also respond to chemicals (Cottrell and Iggo, 1984). In view of the evidence of important roles for intestinal mechano- and chemoreceptors in the control of food intake in other classes of animal, it is likely that such receptors are also important in the ruminant. There are two different types of duodenal chemoreceptor: one is excited by potassium chloride solutions, the response increasing with the concentration of the salt (12.5–450.0 mmolar), while the other is insensitive to potassium chloride but excited by acetic, butyric or propionic acids (10–150 mmolar). The responses elicited were directly related to molecular weight but not to pH or osmolality; both were excited by sodium hydroxide solutions but not usually by sodium bicarbonate. Considerable quantities of potassium ions and VFAs leave the rumen and might, therefore, be expected to stimulate the abomasal and duodenal chemoreceptors and act in the negative feedback control of feeding.
Dynes (1993) studied the effect of duodenal osmolality on feeding in sheep by injecting 5 ml/kg of 6.5% NaCl or mannitol into the duodenum 5 min before feeding and without access to drinking water. There was almost complete inhibition of feeding in the first 15 min, an effect not alleviated by local anaesthetic. When water was made available 30 min after feeding had commenced, the sheep immediately drank a large volume and between 1.5 and 3 h food intake was significantly higher than when water was not available.
The amounts of salt, mannitol and anaesthetics were similar to those used by Houpt et al. (1983), who did find that anaesthetic reversed the intake depression by mannitol in pigs. It seems unlikely that there would be basic differences between the intestinal physiology of pigs and sheep, but no explanation has been proposed for these different experimental results.
In adult ruminants offered dry foods, osmolality can be up to 585 mosmol/kg in the duodenum, but not so high further along the intestines. The osmotic effect of digesta in the duodenum could be an important contributor to satiety under many circumstances, but little relevant research has been carried out with ruminants.
Although there have been suggestions on several occasions that flow through the intestines limits voluntary intake by ruminants, this is not a generally important factor. Suspensions of sawdust or methylcellulose infused into the abomasum at rates which doubled the volume of faecal production had no effect on voluntary food intake and it should be concluded, therefore, that intestinal capacity is not a limiting factor in feeding.
The role of gut hormonessuch as cholecystokinin is covered in Chapter 4.