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Biomedical subjects

N Geary

Publications and source records attributed to N Geary.

At least 37 records · Page 2Linked to original sources
PubMed1998

Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats.

The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3 through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g (or 13-20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.

Animals↗
PubMed1998

Chronic administration of OB protein decreases food intake by selectively reducing meal size in female rats.

The mechanisms by which OB protein controls food intake and energy balance are unknown. Therefore, we investigated the effects of a novel modified human recombinant OB protein (Mod-OB) on spontaneous feeding patterns, body weight, running wheel activity, and ovarian cycling in female rats. Mod-OB or vehicle was injected (4 mg . kg-1 . day-1 sc) for 2 ovarian cycles (8 days) using a within-subjects design. Observations were continued for five ovarian cycles after injections; treatments were then reversed. Mod-OB reduced food intake approximately 20% from injection day 1 to postinjection day 2. Body weight was reduced from injection day 3 to postinjection day 15 (maximum decrease, 25 +/- 4 g, postinjection days 3 and 4). Food intake was reduced due to decreases in nocturnal meal size, which appeared to be superimposed on the normal pattern of spontaneous feeding (i.e., reductions in meal size at estrus). Mod-OB did not significantly affect diurnal food intake or meal patterns, failed to alter wheel running, and did not disrupt the rats' ovarian cycles. We conclude that chronically administered Mod-OB reduces food intake in female rats by selectively affecting the mechanisms controlling meal size.

Analysis of Variance↗
PubMed1998

The effect of estrogen on appetite.

Such eating disorders as anorexia nervosa, bulimia nervosa, and binge eating disorder are associated with significant morbidity and mortality in women. The etiology of these disorders and the causes of women's increased vulnerability to them remain obscure. The lack of understanding of the biological bases of normal and abnormal human eating behavior impedes development of effective pharmacologic treatment for eating disorders. A review of basic research, implicating estradiol in the physiologic control of eating in laboratory animals, shows potential heuristic and mechanistic significance for normal and disordered eating in women. Furthermore, accumulating evidence indicates that estradiol may decrease meal size by increasing the potency of the satiating actions of some gut peptides, especially cholecystokinin. These findings suggest there may be hope for treatment through manipulation of estradiol's interactions with both peripheral psychological and central neural controls of eating.

Animals↗
PubMed1997

Ovariectomy and estradiol affect postingestive controls of sucrose licking.

Ovariectomy (OVX) has been shown to increase, and estradiol replacement to decrease, meal size in rats. Because little is known about how estradiol influences meals, we conducted two experiments to examine the effects of OVX and beta-estradiol 3-benzoate (EB) replacement on the microstructure of licking behavior. In both experiments, patterns of licking were analyzed in adult female Sprague-Dawley rats during an 0.8 M sucrose test meal. In Experiment 1, meal microstructure was determined preOVX and 10-12 days postOVX. Rate of licking following OVX was not changed during min 1 of the meal, but was significantly faster during min 2-4 of the meal (p < 0.03). The numbers of bursts (runs of licks separated by 250-500 ms) and numbers of clusters (runs of licks separated by > 500 ms) were significantly increased during min 2-4 (p < 0.05). In Experiment 2, OVX rats received EB replacement. Rate of licking after EB replacement was not changed during min 1 of the meal, but was significantly slower during the remainder of the meal (min 2-4, min 5-7, and min 8-10). Burst size, cluster size, and interburst interval were less after EB replacement during min 5-7 of the test meal (all p < 0.05). Because both OVX and EB replacement failed to alter the rate of licking during min 1, estrogen did not appear to alter the palatability of sucrose. OVX and EB replacement did appear to affect a postingestive mechanism(s) that is engaged within 2-4 min of meal onset.

Animals↗
PubMed1997

The satiating potency of hepatic portal glucagon in rats is not affected by [corrected] insulin or insulin antibodies.

To characterize the interactive effects of acute prandial manipulations of insulin and glucagon on spontaneous feeding in adult male rats fed ad lib, glucagon (G) and insulin (1) or insulin antibodies (IAb) were confused into the hepatic portal vein during the first meal of the dark phase. Infusions (3-6 min, 33 microliters/min) were remotely controlled, and a computerized system recorded meal patterns. In Experiment 1, five separate factorial designs were used to test the effects of G (1.3 or 13 micrograms/meal) alone, I (1.3 or 2.7 mU/meal) alone, or both G + I. The peptides were infused either simultaneously or sequentially (G before I). The larger dose of G alone reduced meal size. I neither inhibited feeding nor increased the effects of either G dose. In one test, 13 micrograms/meal G did not block meal size when followed by 2.7 mU I, but this antagonism did not occur in a replication. In several tests, there was a trend for I to decrease the size of the spontaneous meal that followed the meal during which I was infused, but this was statistically significant only once. Intermeal intervals were not affected in any test. Experiment 2 tested coinfusions of 20 micrograms G and polyclonal IAb with an in vitro binding capacity of 40 mU rat insulin. G alone reduced meal size, IAb alone increased meal size, and G + IAb produced an additive effect. These data extend previous investigations of the satiating action of G and I in the rat and indicate 1. that exogenous I does not affect the satiating potency of G; 2. that exogenous G and endogenous I elicit an additive synergistic inhibition of spontaneous meal size; and 3. that G-induced I secretion does not mediate the satiating effect of G.

Animals↗
PubMed1996

The increased satiating potency of CCK-8 by estradiol is not mediated by upregulation of NTS CCK receptors.

Estradiol benzoate (EB) increases the satiating effect of CCK-8 in ovariectomized rats. It is possible that this effect of EB is due to upregulation of CCKA receptors in the terminals of vagal afferent fibers because these receptors have been implicated in the mediation of the satiating effect of intraperitoneally injected CCK-8. To test this hypothesis, we used in vitro quantitative autoradiography to measure the effects of EB on the binding characteristics of CCK receptors in the nucleus tractus solitarius (NTS), a region that contains central terminal projections of abdominal vagal afferent fibers. As additional measures of EB's effects on CCK receptors, we also characterized EB's effects on CCK.8 binding in the area postrema (AP), a brain region rich in CCKA receptors, the ventromedial hypothalamus (VMH), a region rich in CCKB receptors, and in the pancreas, a gland rich in CCKA receptors. Saturation binding experiments were run using [125I]CCK-8 (approximately 40 pM, 2200 Ci/mmol) and 0.1-100 nM unlabelled CCK-8. EB did not change the number (Bmax) or affinity (Kd) of CCK receptors in the NTS. Furthermore, competition experiments with 500 nM of the selective CCKA receptor antagonist devazepide or the selective CCKB antagonist L365,260 demonstrated that EB failed to affect CCK receptor subtype number in the medial and lateral divisions of the NTS. EB also did not affect binding in the AP or VMH. These results do not confirm our hypothesis. The lack of effect of EB on vagal CCKA receptors in the NTS was not due to inappropriate conditions of tissue sampling or autoradiographic technique because EB increased the number, but not the affinity, of CCKA receptors in the pancreas significantly.

Animals↗
PubMed1996

Vena caval bombesin infusion decreases spontaneous meal size in undisturbed rats.

The amphibian tetradecapeptide bombesin (BN) decreases food intake in both humans and animals. Studies have typically examined the effects of BN on scheduled meals in deprived subjects. To investigate the properties of this peptide under more naturalistic conditions, we examined the effects of BN in spontaneously feeding rats. Undisturbed, ad lib-fed male rats (n = 9) with chronic inferior vena caval catheters were infused with saline vehicle and each of 3 doses (2, 4, and 8 micrograms/kg) of BN in counterbalanced order with intervening noninfusion days. Infusions were remotely activated at the onset of the first nocturnal meal and continued for 3 min (34 microliters/min), delivery being completed within the first 2 min of infusion. Feeding was measured via electronic balances linked to a computer. All doses of the peptide significantly decreased the size and duration of the first nocturnal meal. In addition, 4 and 8 micrograms/kg of BN significantly shortened the intermeal interval from the end of the first meal to the beginning of the second meal. Despite this, the satiety ratio (interval/meal size) tended to increase after BN and was significantly increased by the highest dose (8 micrograms/kg), thus indicating a sustained satiety action of the peptide. In summary, these results show that brief, meal-contingent intravenous infusions of BN potently inhibit spontaneous feeding in undisturbed rats.

Animals↗
PubMed1996

Brief, meal-contingent infusions of gastrin-releasing peptide1-27 and neuromedin B-10 inhibit spontaneous feeding in rats.

We have previously shown that brief, meal-contingent infusions of the amphibian peptide bombesin (BN) reduce meal size in spontaneously feeding rats. These inhibitory effects presumably reflect actions of BN on receptors for its mammalian homologues, which include gastrin-releasing peptide1-27 (GRP) and neuromedin B-10 (NMB). In the present study, we used the spontaneous feeding paradigm to explore the effects of meal-contingent infusions of these mammalian homologues. Undisturbed, ad lib-fed male rats (n = 12) with chronic inferior vena caval catheters were infused with saline, 5 nmol/kg GRP, 5 nmol/kg NMB, and a mixture of 5 nmol/kg GRP and 5 nmol/kg NMB in counterbalanced order, with intervening noninfusion days. Infusions were remotely activated at the onset of the first nocturnal meal and continued for 3 min (34 microliters/min), delivery being completed within the first 2 min of infusion. Feeding was measured via electronic balances linked to a computer. The effects of all peptide conditions were confined to the first nocturnal meal. Significant and comparable decreases in the size and duration of this meal were observed with GRP, NMB, and GRP + NMB, with no significant effects on the intermeal interval or satiety ratio (intermeal interval/meal size). Thus, brief vena caval infusions of GRP and NMB, given alone or together at the onset of the first nocturnal meal, significantly reduced meal size and duration in spontaneously feeding rats.

Animals↗
PubMed1995

Estradiol interacts with gastric or postgastric food stimuli to decrease sucrose ingestion in ovariectomized rats.

The sham feeding preparation was used to determine whether systemic estradiol administration inhibits the intake of 0.8 M sucrose of ovariectomized rats by decreasing the potency of pregastric controls of ingestion. During real feeding, significant reductions in the sucrose intake of estradiol-treated rats appeared within 5-6 min. In contrast, estradiol had no effect on sham feeding at any time. The lack of effect of estradiol on sham feeding indicates that pregastric stimuli are not sufficient to mediate the inhibitory effect of estradiol on feeding in ovariectomized rats. Rather, because estradiol did inhibit real feeding, gastric and/or postgastric food stimuli are necessary for this inhibitory effect. The rapid onset of estradiol's inhibitory effect on real feeding suggests that these postingestive stimuli are selective for controls of the initial phase of the meal.

Animals↗
PubMed1995

Amylin decreases meal size in rats.

Adult male rats were intraperitoneally (i.p.) injected with 1.0 microgram/kg amylin at the beginning of the dark phase in 24 h food deprived or undeprived rats, and a computerized system measured feeding behavior. In food deprived rats, amylin reduced the size of the first postdeprivation meal without affecting intrameal feeding rate or the size or timing of subsequent meals. The same pattern was observed in undeprived rats, but amylin also increased the latency to the first postinjection meal. In a conditioned taste aversion test, i.p. amylin (1 microgram/kg) injection just prior to rats' first access to a saccharine-flavored version of their maintenance diet, failed to affect their subsequent selection of that diet relative to the maintenance diet 2 d later. Finally, 2-min meal-contingent hepatic portal infusions of amylin (1-3.2 microgram/rat) during nocturnal spontaneous meals in undisturbed, ad lib fed rats reduced the meal size and meal duration, and increased the postprandial satiety ratio. Again, feeding rate and the size and duration of subsequent meals were not affected. These results suggest that amylin inhibits feeding by facilitating meal-ending satiety processes.

Amyloid↗
PubMed1995

Meal pattern analysis in rats reveals partial agonist activity of the bombesin receptor antagonist BW2258U89.

The spontaneous feeding behavior of adult male rats was monitored during continuous infusion of the bombesin receptor antagonist BW2258U89 into the coeliac artery (100 micrograms kg-1 h-1) from an osmotic minipump. Nocturnal food intake was suppressed over 5 days of testing. Similar effects followed acute BW2258U89 treatment [100 micrograms kg-1, intraperitoneally (i.p.)]. Moreover, i.p. BW2258U89 mimicked the acute behavioral effects of 2 micrograms kg-1 i.p. bombesin by reducing meal size. Verifying that BW2258U89 can retain its potency throughout the entire period of chronic infusion, we demonstrated that the acute anorectic action of bombesin (4 micrograms kg-1, i.p.) was blocked by pretreatment with a BW2258U89 solution (100 micrograms ml-1 kg-1, i.p.) that was freshly prepared, or incubated for 1 or 6 days at body temperature. These data demonstrate that acute and chronic administration of BW2258U89, at a dose that abolishes the satiety effect of bombesin, significantly suppresses spontaneous feeding. Thus, BW2258U89 appears to attenuate food intake by acting as a partial agonist at peripheral receptors for bombesin-like peptides.

Amino Acid Sequence↗
PubMed1995

Hepatic portal insulin antibody infusion increases, but insulin does not alter, spontaneous meal size in rats.

To investigate the acute effects of pancreatic insulin on spontaneous feeding in rats fed ad libitum, insulin or insulin antibodies were infused into the hepatic portal vein during the first meal of either the light or dark phase. Infusions (3 min, 0.033 ml/min) were remotely controlled, and a computerized system recorded meal patterns. In separate crossover tests, 1, 2, 4, 8, and 16 mU insulin/meal did not affect meal size or subsequent intermeal interval (P > 0.10). In one test, nocturnal meal duration was decreased by 2 mU insulin/meal (19%, P < 0.05). Infusions of polyclonal antibodies to human insulin with in vitro rat insulin binding capacity of 20 or 50 mU increased the size of the first nocturnal meal by 24 and 29% (P < 0.05), respectively. Meal duration was reliably increased only by the smaller antibody dose. Subsequent intermeal interval was unaffected by either antibody dose. The stimulatory effect of insulin antibody infusion on meal size indicates that antagonism of circulating insulin during meals interferes with the control of meal termination. Thus insulin appears to play a role in the physiological control of nocturnal spontaneous feeding in rats. Exogenous insulin may have failed to decrease meal size because of a ceiling effect.

Animals↗
PubMed1994

Cyclic estradiol replacement increases the satiety effect of CCK-8 in ovariectomized rats.

The influence of cyclic ovarian hormone replacement therapy on the satiety effect of exogenous CCK-8 was determined to investigate the mechanism mediating the preestrous decrease in meal size in female rats. Once weekly, food-deprived ovariectomized rats were IP injected with 0.5-4 micrograms/kg CCK-8 and offered 0.4-0.8 M sucrose 52 h after the second of two daily SC injections of 2.5 or 10 micrograms estradiol benzoate or vehicle and 4 h after 500 mg progesterone or vehicle. In each of three tests, estradiol significantly increased CCK-8's inhibitory effect on sucrose intake. In contrast, progesterone alone or in combination with estradiol did not consistently influence the satiating potency of CCK-8. The interaction of estradiol and CCK-8 was clearest for the dose of 4 micrograms/kg CCK-8. The interaction occurred during diurnal tests and during dark-onset tests in which estradiol did not decrease baseline sucrose intake. These results demonstrate that a cyclic regimen of estradiol replacement in ovariectomized rats is sufficient to enhance the satiating effect of exogenous CCK-8 and that simultaneous progesterone treatment does not influence this effect. Potentiation of the satiating effect of CCK released from the small intestine by ingested food may be one of the mechanisms by which food intake decreases during the period of high estrogen concentration in the estrus cycle.

Animals↗
PubMed1994

Caprine arthritis encephalitis virus infection changes caprine blood monocyte responsiveness to lipopolysaccharide stimulation in vitro.

The effects of caprine arthritis encephalitis virus (CAEV) infection on cytokine activity of caprine monocytes stimulated with Escherichia coli lipopolysaccharide (LPS) were examined. Compared with supernatants from LPS-stimulated monocytes of CAEV-negative goats, supernatants from CAEV-positive goats stimulated less proliferation of murine thymocytes in the MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay, showed about 50% less IL-1 activity on the IL-1-dependent cell line LBRM-33 1 A-5, and showed about 200% more tumor necrosis factor (TNF) activity on the TNF-sensitive murine fibroblast cell line L-929. These results indicate that CAEV infection changes caprine monocyte cytokine responsivity.

Animals↗
PubMed1993

Glucagon acts in the liver to control spontaneous meal size in rats.

To determine the site of origin of pancreatic glucagon's inhibitory effect on spontaneous feeding in rats, glucagon was infused into either the hepatic portal vein or the inferior vena cava during spontaneous meals late in the dark phase. Hepatic portal infusion of 1.7-13.6 micrograms glucagon/meal reduced spontaneous meal size. In contrast, these doses did not significantly affect meal size when delivered via vena caval catheters that ended near the junction of the hepatic vein. This difference indicates that glucagon receptor sites in the liver initiate the satiating action of glucagon during spontaneous meals. The vagal dependency of glucagon satiety was also tested. Hepatic portal infusion of 13.6 micrograms glucagon/meal reduced the size of spontaneous meals both early and late in the dark in neurally intact rats, but not in hepatic-vagotomized rats. Finally, antagonism of endogenous glucagon with hepatic portal infusion of glucagon antibodies in a dose sufficient to neutralize 1 ng glucagon in vitro increased spontaneous meal size in intact rats, but not in hepatic-vagotomized rats. Thus the satiating effects of both exogenous and endogenous glucagon on spontaneous food intake appear to depend on the hepatic branch of the vagus. Taken together, these results are consistent with the hypothesis that glucagon acts in the liver to produce a satiety signal that is transmitted to the brain by the hepatic branch of the abdominal vagus.

Animals↗