Suppression of meal size by intestinal nutrients is eliminated by celiac vagal deafferentation

Abstract

The arrival of nutrients in the gastrointestinal tract suppresses intake. To specify the neural pathways and receptor locations of this feedback, we examined the effects of intraduodenal infusions of 10 nutrients plus saline on short-term food intake of rats with selective deafferentations of vagal celiac branches. Three response profiles were observed: 1) isotonic saline, 5.6% glycerol, and 3% fructose did not inhibit intake of controls or selectively deafferented animals; 2) 3% glucose, 3% maltose, 3% L-phenylalanine, 12% Isocal, and 1.4% oleic acid suppressed intake of controls, but this inhibition was eliminated by vagal celiac deafferentation; and 3) 3% casein hydrolysate and 24% Isocal suppressed intake of controls and rats with selective vagotomies, although the latter exhibited significantly less suppression. In addition, elimination of celiac afferents chronically reduced meal size (i.e., first 30-min intake) without reducing daily food intake or body weight. Furthermore, D-phenylalanine infusions produced a delayed suppression of food intake in controls (possibly from intraluminal irritation); however, this reduction was eliminated with celiac deafferentation. Overall, this experiment indicates that vagal celiac afferents are critical for preabsorptive detection of some energy-yielding molecules or properties of nutrient solutions (as well as, perhaps, intraluminal inflammation), but not others, which are still detected, although only partially.

Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal “bitter taste” cue

“…For instance, one study showed that rats did not suppress intake following a preload of sweetener to the stomach (51), while a separate study showed that rats did not develop a preference to a flavor that had been repeatedly paired with GI sweetener infusions (41). Both of these behavioral measures are, however, sensitive to sweettasting caloric substances, like glucose (1,40,41,49,51). Because artificial sweeteners presumably only provide a sweet taste signal (i.e., no calories) in the intestine, it is possible that the typical longer-term behavioral parameters used in preload and flavor preference studies are not well suited to look at rapid Fig.…”

“…This CFP develops even when vagal and/or splanchnic afferents are surgically or chemically disrupted, suggesting nutrients sufficiently engage postabsorptive signals to affect behavior (40,53). At the same time, vagal deafferentation abolishes rapid discrimination of GI stimulus properties for CFP (53) and attenuates the short-term satiating effects of some, but not all, nutrients in the GI tract, suggesting auxiliary information is relayed by preabsorptive receptors (40,49).In addition to illustrating that both preabsorptive and postabsorptive signaling pathways are involved in the postingestive controls of intake, the CFP example highlights yet another consideration with implications for behavioral analyses of GI infusions. Test subjects appear to be quite flexible with respect to selecting different sources of feedback to solve the task.…”

“…This CFP develops even when vagal and/or splanchnic afferents are surgically or chemically disrupted, suggesting nutrients sufficiently engage postabsorptive signals to affect behavior (40,53). At the same time, vagal deafferentation abolishes rapid discrimination of GI stimulus properties for CFP (53) and attenuates the short-term satiating effects of some, but not all, nutrients in the GI tract, suggesting auxiliary information is relayed by preabsorptive receptors (40,49).…”

Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway in Solitary Nucleus Mediates Cholecystokinin-Induced Suppression of Food Intake in Rats

“…The process of satiation that leads to termination of a meal is thought to depend mainly on various signals generated by the interaction of ingested food with the gastrointestinal tract, such as gastric distension and cholecystokinin (CCK) (Gibbs et al, 1973;Smith et al, 1985;Schwartz and Moran, 1996;Smith, 1996;Moran, 2000). Many of these satiety signals reach the nucleus of the solitary tract in the caudal brainstem via vagal sensory nerve fibers (Smith et al, 1985;Walls et al, 1995;Schwartz et al, 1999), where they are integrated with information from the hypothalamus and other forebrain sites to stop additional ingestion (Berthoud, 2004).…”

Voluntary consumption of ethyl oleate reduces food intake and body weight in rats

“…Previously, studies have shown that intraintestinal infusions of long-chain fatty acids significantly reduced voluntary food intake (4,16): the mechanisms that control this response are complex, but likely involve gut-initiated satiety signals (9). Numerous gastrointestinal peptide hormones are released during and immediately after food intake, including cholecystokinin, peptide YY, glucagon-like peptide 1, and oxyntomodulin, which act either distally, signaling satiety and suppressing food intake via receptors located in the central nervous system, or proximally, by slowing gastric emptying (22,27). Importantly, numerous reports have demonstrated that infusions of nutrients directly into the small intestine can activate a satiety mechanism initiated and mediated by the gut (9,16).…”