Effect of nitric oxide synthase inhibitors on short-term appetite and food intake in humans.
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Animal studies suggest that nitric oxide (NO) may be a physiological regulator of appetite; NO synthase (NOS) inhibition suppresses food intake in rats, mice, and chickens. It is not known whether NO has any effect on appetite in humans. We have used NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), both competitive, nonselective inhibitors of NOS, in two separate studies to evaluate the role of NO in the short-term regulation of appetite in humans. In study I, 13 men (18-25 yr) underwent paired studies, in randomized, double-blind fashion, after an overnight fast. L-NMMA (4 mg. kg-1. h-1) or saline (0.9%) was infused intravenously at a rate of 40 ml/h for 1.5 h. In study II, eight men (18-26 yr) underwent three randomized, double-blind studies after an overnight fast. L-NAME (75 or 180 micrograms . kg-1. h-1) or saline (0.9%) was infused intravenously at a rate of 20 ml/h for 120 min. Hunger and fullness were measured using visual analog scales; blood pressure and heart rate were monitored, and 30 min before the end of the infusion, subjects were offered a cold buffet meal. Total caloric intake and the macronutrient composition of the meal were determined. Both L-NMMA (P = 0.052) and L-NAME (P < 0.05; both doses) decreased heart rate, L-NMMA increased diastolic blood pressure (P < 0.01), and L-NAME increased systolic blood pressure (P = 0.052). Neither drug had any effect on caloric intake or sensations of hunger or fullness. Despite having significant effects on cardiovascular function in the doses used, neither L-NMMA nor L-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans. (+info)
Reduced sensitivity to the satiation effect of intestinal oleate in rats adapted to high-fat diet.
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When rats are maintained on high-fat diets, digestive processes adapt to provide for more efficient digestion and absorption of this nutrient. Furthermore, rats fed high-fat diets tend to consume more calories and gain more weight than rats on a low-fat diet. We hypothesized that, in addition to adaptation of digestive processes, high-fat maintenance diets might result in reduction of sensitivity to the satiating effects of fat digestion products, which inhibit food intake by activating sensory fibers in the small intestine. To test this hypothesis we measured food intake after intestinal infusion of oleic acid or the oligosaccharide maltotriose in rats maintained on a low-fat diet or one of three high-fat diets. We found that rats fed high-fat diets exhibited diminished sensitivity to satiation by intestinal infusion of oleic acid. Sensitivity to the satiation effect of intestinal maltotriose infusion did not differ between groups maintained on the various diets. Reduced sensitivity to oleate infusion was specifically dependent on fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. These results indicate that diets high in fat reduce the ability of fat to inhibit further food intake. Such changes in sensitivity to intestinal fats might contribute to the increased food intake and obesity that occur with high-fat diet regimens. (+info)
Blood glucose patterns and appetite in time-blinded humans: carbohydrate versus fat.
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We assessed the extent to which a possible synchronization between transient blood glucose declines and spontaneous meal initiation would lend support to the interpretation of a preload study with isoenergetic (1 MJ) isovolumetric high-fat or simple carbohydrate (CHO) preload drinks. Ten men (18-30 yr) fasted overnight and then were time blinded and made aware that they could request meals anytime. At first meal requests, volunteers consumed a preload; ad libitum meals were offered at subsequent requests. Postabsorptively, transient declines in blood glucose were associated with meal requests (chi(2) = 8.29). Subsequent meal requests occurred during "dynamic declines" in blood glucose after the peak induced by drink consumption (100%). These meal requests took twice as long to occur after high-fat than after CHO preloads (fat = 126 +/- 21, CHO = 65 +/- 15 min), consistent with differences in interpolated 65-min satiety scores (fat = 38 +/- 8.2, CHO = 16 +/- 4). Postprandially, transient blood glucose declines were associated with meal requests (chi(2) = 4.30). Spontaneous meal initiations were synchronized with transient and dynamic blood glucose declines. Synchronization of intermeal interval and dynamic declines related to higher satiating efficiency from high-fat preloads than from simple CHO preloads. (+info)
Dopaminergic correlates of sensory-specific satiety in the medial prefrontal cortex and nucleus accumbens of the rat.
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Changes in dopamine (DA) efflux in the medial prefrontal cortex and nucleus accumbens of rats were monitored using in vivo microdialysis during sensory-specific satiety experiments. Rats consumed significant amounts of a palatable food during an initial meal but ate little when the same food was available as a second meal. In contrast, rats given a different palatable food ate a significant quantity during the second meal. DA efflux in both brain regions reflected this difference in food intake, indicating that DA activity is influenced by changes in the deprivation state of animals and sensory incentive properties of food. Given the proposed role of DA in motivated behaviors, these findings suggest that DA efflux may signal the relative incentive salience of foods and thus is a determinant of the pattern of food consumption observed in sensory-specific satiety. (+info)
Water incorporated into a food but not served with a food decreases energy intake in lean women.
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BACKGROUND: Previous research showed that decreasing the energy density (kJ/g) of foods by adding water to them can lead to reductions in energy intake. Few studies have examined how water consumed as a beverage affects food intake. OBJECTIVE: This study examined the effects of water, both served with a food and incorporated into a food, on satiety. DESIGN: In a within-subjects design, 24 lean women consumed breakfast, lunch, and dinner in our laboratory 1 d/wk for 4 wk. Subjects received 1 of 3 isoenergetic (1128 kJ) preloads 17 min before lunch on 3 d and no preload on 1 d. The preloads consisted of 1) chicken rice casserole, 2) chicken rice casserole served with a glass of water (356 g), and 3) chicken rice soup. The soup contained the same ingredients (type and amount) as the casserole that was served with water. RESULTS: Decreasing the energy density of and increasing the volume of the preload by adding water to it significantly increased fullness and reduced hunger and subsequent energy intake at lunch. The equivalent amount of water served as a beverage with a food did not affect satiety. Energy intake at lunch was 1209 +/- 125 kJ after the soup compared with 1657 +/- 148 and 1639 +/- 148 kJ after the casserole with and without water, respectively. Subjects did not compensate at dinner for this reduction in lunch intake. CONCLUSION: Consuming foods with a high water content more effectively reduced subsequent energy intake than did drinking water with food. (+info)
Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and fos responses to vagal satiety signals.
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To test the possible role of N-methyl-D-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10-30 min, 8.9 +/- 1.0 vs. 2.9 +/- 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (-75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals. (+info)
Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors.
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Adult Otsuka Long-Evans Tokushima fatty (OLETF) rats lack functional cholecystokinin A (CCK-A) receptors, are diabetic, hyperphagic, and obese, and have patterns of ingestion consistent with a satiety deficit secondary to CCK insensitivity. Because dietary fat potently stimulates CCK release, we examined how dietary fat modulates feeding in adult male OLETF rats and their lean [Long-Evans Tokushima (LETO)] controls. High-fat feeding produced sustained overconsumption of high-fat diet (30% corn oil in powdered chow) over a 3-wk period in OLETF but not LETO rats. We then assessed the ability of gastric gavage (5 ml, 1-2 kcal/ml x 15 s) or duodenal preloads (1 kcal/ml, 0.44 ml/min x 10 min) of liquid carbohydrate (glucose), protein (peptone), or fat (Intralipid) to suppress subsequent 30-min 12.5% glucose intake in both strains. In OLETF rats, gastric and duodenal fat preloads were significantly less effective in suppressing subsequent intake than were equicaloric peptone or glucose. These results demonstrate that OLETF rats fail to compensate for fat calories and suggest that their hyperphagia and obesity may stem from a reduced ability to process nutrient-elicited gastrointestinal satiety signals. (+info)
Cocaine- and amphetamine-regulated transcript in the rat vagus nerve: A putative mediator of cholecystokinin-induced satiety.
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Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the central nervous system. Recent studies have pointed to a role for CART-derived peptides in inhibiting feeding behavior. Although these actions have generally been attributed to hypothalamic CART, it remains to be determined whether additional CART pathways exist that link signals from the gastrointestinal tract to the central control of food intake. In the present study, we have investigated the presence of CART in the rat vagus nerve and nodose ganglion. In the viscerosensory nodose ganglion, half of the neuron profiles expressed CART and its predicted peptide, as determined by in situ hybridization and immunohistochemistry. CART expression was markedly attenuated after vagotomy, but no modulation was observed after food restriction or high-fat regimes. A large proportion of CART-labeled neuron profiles also expressed cholecystokinin A receptor mRNA. CART-peptide-like immunoreactivity was transported in the vagus nerve and found in a dense fiber plexus in the nucleus tractus solitarii. Studies on CART in the spinal somatosensory system revealed strong immunostaining of the dorsal horn but only a small number of stained cell bodies in dorsal root ganglia. The present results suggest that CART-derived peptides are present in vagal afferent neurons sensitive to cholecystokinin, suggesting that the role of these peptides in feeding may be explained partly by mediating postprandial satiety effects of cholecystokinin. (+info)