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R J Seeley

Publications and source records attributed to R J Seeley.

At least 91 records · Page 5Linked to original sources
PubMed1996

Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice.

Correction of the obese state induced by genetic leptin deficiency reduces elevated levels of both blood glucose and hypothalamic neuropeptide Y (NPY) mRNA in ob/ob mice. To determine whether these responses are due to a specific action of leptin or to the reversal of the obese state, we investigated the specificity of the effect of systemic leptin administration to ob/ob mice (n = 8) on levels of plasma glucose and insulin and on hypothalamic expression of NPY mRNA. Saline-treated controls were either fed ad libitum (n = 8) or pair-fed to the intake of the leptin-treated group (n = 8) to control for changes of food intake induced by leptin. The specificity of the effect of leptin was further assessed by 1) measuring NPY gene expression in db/db mice (n = 6) that are resistant to leptin, 2) measuring NPY gene expression in brain areas outside the hypothalamus, and 3) measuring the effect of leptin administration on hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Five daily intraperitoneal injections of recombinant mouse leptin (150 micrograms) in ob/ob mice lowered food intake by 56% (P < 0.05), body weight by 4.1% (P < 0.05), and levels of NPY mRNA in the hypothalamic arcuate nucleus by 42.3% (P < 0.05) as compared with saline-treated controls. Pair-feeding of ob/ob mice to the intake of leptin-treated animals produced equivalent weight loss, but did not alter expression of NPY mRNA in the arcuate nucleus. Leptin administration was also without effect on food intake, body weight, or NPY mRNA levels in the arcuate nucleus of db/db mice. In ob/ob mice, leptin did not alter NPY mRNA levels in cerebral cortex or hippocampus or the expression of CRH mRNA in the hypothalamic paraventricular nucleus (PVN). Leptin administration to ob/ob mice also markedly reduced serum glucose (8.3 +/- 1.2 vs. 24.5 +/- 3.8 mmol/l; P < 0.01) and insulin levels (7,263 +/- 1,309 vs. 3,150 +/- 780 pmol/l), but was ineffective in db/db mice. Pair-fed mice experienced reductions of glucose and insulin levels that were < 60% of the reduction induced by leptin. The results suggest that in ob/ob mice, systemic administration of leptin inhibits NPY gene overexpression through a specific action in the arcuate nucleus and exerts a hypoglycemic action that is partly independent of its weight-reducing effects. Furthermore, both effects occur before reversal of the obesity syndrome. Defective leptin signaling due to either leptin deficiency (in ob/ob mice) or leptin resistance (in db/db mice) therefore leads directly to hyperglycemia and the overexpression of hypothalamic NPY that is implicated in the pathogenesis of the obesity syndrome.

Animals↗
PubMed1995

Effect of occluding the pylorus on intraoral intake: a test of the gastric hypothesis of meal termination.

Meal size does not change in response to food being restricted to the stomach by occlusion of the pylorus. This result has been used as evidence for a gastric model of meal termination where feedback arising solely from the stomach is taken to underlie satiation. Such data provide support for the gastric model, however, only if the rate of gastric emptying during ingestion in the unoccluded condition is slow, such that comparable amounts of food would be found in the stomach at the end of the meal in both the pylorus-occluded and unoccluded conditions. To evaluate this tissue directly, rats were implanted with pyloric cuffs and gastric cannulas and given an intraoral intake test of a 10.5% glucose solution with either the pylorus occluded or unoccluded. At the end of each intraoral intake test, the content of the stomach was removed via the gastric cannula and it's volume and concentration measured. Occlusion of the pylorus did not change meal size, but both the volume and grams of glucose solute found in the stomach were substantially greater in the pylorus-occluded condition. These results are not consistent with the hypothesis that the stomach is the sole source of inhibitory signals that terminate a meal. Cumulative intake would appear to be accurately tracked regardless of its distribution within the digestive tract.

Animals↗
PubMed1995

Discriminative cues produced by NPY do not generalize to the interoceptive cues produced by food deprivation.

Exogenous administration of neuropeptide Y (NPY) into the third ventricle causes a rapid and robust feeding response in sated rats. The current experiment was designed to assess whether the interoceptive cues produced by exogenous NPY administration generalize to those produced by another orexigenic treatment: 24-h food deprivation. Rats were placed in a chamber after receiving either NPY or saline infused into the third ventricle for a total of six sessions (three after NPY and three after saline). Half of the rats were given a brief foot shock after NPY and not after saline, while the other half received the opposite contingency. The pattern of behavioral immobility for the two groups differed with the rats "freezing" significantly more to the treatment (NPY or saline) paired with shock. Then rats were tested for generalization by placing them in the chamber either after 0- or 24-h food deprivation with no NPY or saline administration or any foot shock. Behavioral immobility during the generalization test of rats that had been trained with shock following saline was greater than that for rats that had been trained with shock following NPY, independent of whether testing occurred when the rats were 0- or 24-h food deprived. This outcome indicates that interoceptive stimuli produced by NPY are no more similar to internal cues produced by 24-h food deprivation than to the stimulus consequences of ad lib feeding. These and other recent findings suggest that food deprivation activates processes or mechanisms different from those that underlie the orexigenic effects of NPY.

Animals↗
PubMed1995

Intraventricular insulin enhances the meal-suppressive efficacy of intraventricular cholecystokinin octapeptide in the baboon.

Chronic intraventricular (IVT) insulin infusion suppresses food intake and body weight in the baboon. It has been hypothesized that one mechanism of this action may be enhancement of the effectiveness of satiety factors that regulate meal size. This hypothesis was supported by prior demonstration of a shift in the meal-suppressive effectiveness of cholecystokinin octapeptide (CCK-8) which was given intravenously. The authors tested the effectiveness of a near threshold dose of CCK-8 (25 ng/kg) given via the lateral ventricles (IVT) prior to a 30-min meal, while baboons were chronically infused with cerebrospinal fluid or insulin (100 microU/day) via the lateral ventricles. IVT CCK-8 infusion resulted in meal size changes of -44 +/- 7% and -75 +/- 9% in the absence and presence of insulin, respectively; this was observed in each of the three animals studied. These results provide further support for the hypothesis that IVT insulin can interact with other, meal-regulatory, peptides.

Animals↗
PubMed1995

Whole body energy expenditure and fuel oxidation after 2,5-anhydro-D-mannitol administration.

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) increases food intake in nondeprived rats. Several lines of evidence indicate that vagal signals arising from the liver are critical for this effect. In addition, 2,5-AM decreases plasma glucose and increases lipolysis, resulting in an increase in plasma free fatty acids and ketone bodies. In these respects 2,5-AM produces a state analogous to that observed after food deprivation. Using an indirect calorimeter, we determined that 2,5-AM (300 mg/kg ip) causes a potent and long-lasting decrease in respiratory quotient, indicating a decrease in the fraction of total energy derived from carbohydrate oxidation and an increase in the fraction derived from fatty acid oxidation. These metabolic variables were altered without affecting total metabolic rate. This dose of analogue also stimulated significantly greater food intake than injections of vehicle. These results support the continued use of 2,5-AM as a tool to probe the metabolic controls of food intake.

Analysis of Variance↗
PubMed1995

Neuropeptide Y fails to increase intraoral intake in rats.

Neuropeptide Y (NPY) has a potent orexigenic effect when administered either into the third ventricle or directly into hypothalamic nuclei, but the mechanism by which NPY increases intakes is poorly understood. The present study tested the ability of NPY to increase intake of the rat in the intraoral intake test, which focuses on the highly stereotyped consummatory phase of ingestion by introducing a 0.1 M sucrose solution directly into the oral cavity of rats via indwelling intraoral cannulas. Doses of 3, 9.5, and 30 micrograms of NPY, when administered into the third ventricle, all failed to change intraoral intake compared with a saline control. Food deprivation (24 h), however, nearly doubled intraoral intake. Additionally, in separate experiments, 9.5 micrograms of NPY significantly increased both 1-h food intake and 1-h bottle intake of 0.1 M sucrose. These results are consistent with two conclusions. 1) NPY does not affect the consummatory phase of ingestion. 2) NPY administration does not completely mimic the stimulus state associated with food deprivation, since food deprivation but not NPY administration increases intake in the intraoral intake test.

Animals↗
PubMed1995

NPY increases food intake in white-crowned sparrows: effect in short and long photoperiods.

To determine if altered sensitivity to neuropeptide Y (NPY) underlies premigratory fattening, white-crowned sparrows held on short day length (9:15-h light-dark) received injections into the third ventricle (ivt) of saline or several doses of NPY. An inverted-U function occurred with food intake increasing 30 and 60 min after doses of 1.0 and 2.0 micrograms NPY. When photostimulated (20:4-h light-dark), birds increased daily caloric intake and gained weight rapidly. Birds maintained on long day lengths significantly increased food intake after 0.25 and 0.5 micrograms of NPY and did not respond to higher doses. The effective dose range for NPY to increase food intake moved to the left, suggesting an increase in sensitivity to the peptide on long day lengths. In summary, white-crowned sparrows consume more food when administered NPY ivt and have increased sensitivity when photostimulated and gaining weight. Hence NPY may be a natural stimulator of food intake in this species.

Animals↗
PubMed1995

Regulation of food intake by metabolic fuels in white-crowned sparrows.

Migratory birds rely on increased fat storage and fatty acid utilization to meet seasonal changes of energy expenditure and as a result increase food intake and fat stores before migration. To determine whether their feeding behavior is sensitive to carbohydrate and/or fatty acid utilization, white-crowned sparrows maintained on short daylength (9L15D) were injected intraperitoneally with 2-deoxy-D-glucose (2-DG) or 2,5-anhydro-D-mannitol (2,5-AM). Low doses of 2-DG (25 or 50 mg/kg) had no effect on food intake, and higher doses (100 or 300 mg/kg) significantly suppressed feeding after 1 and 2 h. No dose of 2-DG increased meal size. Similarly, low doses of 2,5-AM (25, 50, or 100 mg/kg) had no effect on food intake, and higher doses (300 and 600 mg/kg) significantly suppressed intake. These data suggest that decreased carbohydrate metabolism does not elicit feeding in this species. Importantly, these drugs, as well as insulin and glucagon, were demonstrated to increase plasma fatty acids as well as to decrease feeding. Injections of tributyrin (100, 300, 600, or 2,000 mg/kg i.p.) or glycerol (300, 450, and 600 mg/kg) also significantly suppressed 60-min and 120-min food intake dose dependently in these birds, and equimolar glucose (1,200 mg/kg) had no effect. We conclude that feeding by the white-crowned sparrow is unresponsive to manipulations of carbohydrate metabolism and is decreased after manipulations that increase plasma lipids.

Animals↗
PubMed1995

Forebrain contribution to the induction of a cellular correlate of conditioned taste aversion in the nucleus of the solitary tract.

A conditioned taste aversion (CTA) is a form of classical conditioning in which animals avoid a taste (conditioned stimulus; CS) which has been previously paired with a treatment (unconditioned stimulus; US) that produces transient illness. Recently, a reliable cellular correlate of the behavioral expression of a CTA was identified using c-Fos immunostaining as a marker of neuronal activation. Exposure to a saccharin solution (CS) which had previously been paired with lithium chloride (LiCl; US) induced significant c-Fos-like immunoreactivity (c-FLI) in the intermediate zone of the nucleus of the solitary tract (NTS), a response that was quite similar to that displayed following administration of LiCl alone. The present studies employed a variant of the chronic decerebrate rat preparation to explore whether circuitry intrinsic to the brainstem is sufficient for the induction of c-FLI in both as an unconditioned response to the LiCl and as a conditioned response to the saccharin. Using chronic hemidecerebrate rats, which have a unilateral brain transection at the level of the superior colliculus, we found that the unconditioned c-FLI to LiCI was unaltered by the transection, while the conditioned expression of c-FLI to the CS taste was evident only on the side of the NTS which retained neural connections with the forebrain. These findings strongly implicate forebrain input in this cellular correlate of CTA learning and also indicate that the pathways mediating the response to the US (LiCl) and the CS (saccharin) differ.

Animals↗
PubMed1995

A comparison between effects of intraventricular insulin and intraperitoneal lithium chloride on three measures sensitive to emetic agents.

When low doses of insulin are infused directly into the third ventricle, rats reduce their food intake and lose weight. To determine whether these effects could be due to malaise induced by the treatment, the effects of intraventricular insulin were compared to the effects of the emetic agent lithium chloride to condition a taste aversion, to stimulate oxytocin secretion, and to reduce sodium appetite in response to furosemide treatment. For all three of these measures, lithium chloride treatment had a predictable effect compared to controls. Specifically, lithium caused a significant taste aversion, elevated plasma oxytocin, and attenuated sodium appetite. However, lithium did not produce a significant change in food intake or body weight. On the other hand, intraventricular insulin treatment did cause a significant reduction in body weight yet had no effect on these indices of malaise in the rat. These data are consistent with the hypothesis that intraventricular insulin does not reduce food intake and body weight by producing malaise but rather serves as a negative feedback signal of body adiposity to the central nervous system.

Animals↗
PubMed1994

Neurological dissociation of gastrointestinal and metabolic contributions to meal size control.

A method was developed to separate gastrointestinal (GI) and metabolic contributions to meal size and applied to intact and chronic decerebrate (CD) rats. The effect of a 10-ml milk diet preload or 24 hr of food deprivation on the consumption of a 0.1-M sucrose solution was compared with intake in a no-deprivation/no-preload condition. In the no-deprivation/no-preload condition, rats were given their normal complement of feedings but had the contents of their stomachs removed via a gastric cannula before the intake test. Compared with the no-deprivation/no-preload condition, intact and CD rats consumed significantly less after the preload, but only intact rats ate more after deprivation. Thus intact rats were sensitive to both GI and metabolic influences on intake, whereas CD rats responded to only the GI manipulation. The experiments showed that GI and metabolic contributions to the deprivation response are mediated by neural structures that are at least partly nonoverlapping. The GI component is likely to be contained within the caudal brainstem. The neural systems required for the response to the metabolic changes accompanying deprivation appear to be more widely distributed.

Animals↗
PubMed1994

A behavioral probe of the growth of intake potential during the inter-meal interval in the rat.

The rat's willingness to ingest glucose after an initial intraoral intake test was probed by beginning a 2nd intraoral intake test at variable durations (1-120 min). In Experiment 1, after an initial meal of 12.5% glucose solution averaging 26.9 +/- 1.7 ml (SEM, n = 10), the size of the 2nd (probe) meal of the same stimulus increased linearly from 4.0 +/- 0.9 ml after a 1-min delay to 15.4 +/- 2.7 ml after a 120-min delay. In Experiment 2, intraoral intake of a more concentrated (37.5%) glucose solution rose more slowly as a function of delay from 2.4 +/- 2.7 ml (SEM, n = 12) to 4.9 +/- 0.6 ml. For each glucose concentration, the linear recovery function and a slope that depends on stimulus concentration are consistent with a role for gastric emptying during the delay in intake recovery. In Experiment 3, rats ingested 12.5% or 37.5% glucose to satiety in an initial test and received, after a variable delay, either the same or the other concentration as the probe stimulus. The same volumes were ingested at each delay whether the glucose concentration of the probe stimulus was the same or was switched from that presented in the initial test. This result shows that the taste and caloric properties of the probe stimulus played no role in determining how much of it would be ingested. Rather, the satiety criterion for the probe test was reached on the basis of the volume ingested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Lesions of the central nucleus of the amygdala. I: Effects on taste reactivity, taste aversion learning and sodium appetite.

Bilateral damage to the central nucleus of the amygdala (CeAX) in the rat blunts need-induced NaCl intake and abolishes daily need-free NaCl intake when measured with a two-bottle test. Such a deficit could be the result of impaired taste function. To assess the taste function of the CeAX rat various taste stimuli were introduced directly into the oral cavity and taste-elicited oral motor responses were measured. Oral motor responses elicited by 0.62 M and 0.13 M sodium chloride, 0.3 M sucrose and 0.01 M citric acid, were similar in control and CeAX rats. Additionally CeAX and control rats acquired a taste aversion for fructose or maltose when either was paired with LiCl. Finally, in CeAX rats, like in control rats, the pattern of oral motor responses to 0.5 M NaCl was dependent on internal state; sodium depletion dramatically altered taste-elicited oral motor behavior. These results suggest that, in the rat, the deficits in NaCl intake behavior that follow CeAX do not appear to be a result of dramatic changes in gustatory function.

Amygdala↗
PubMed1993

Lesions of the central nucleus of the amygdala. II: Effects on intraoral NaCl intake.

Bilateral lesions of the central nucleus of the amygdala (CeAX) disrupt both need-free and need-induced NaCl intake. Quite surprisingly, in response to sodium depletion, the same rats who fail to augment their NaCl consumption dramatically increase the numbers of oral motor behaviors associated with ingestion that they display when NaCl is presented intraorally. The present study attempts to resolve these apparently contradictory results by measuring the intake of a NaCl solution delivered directly into the mouth. Controls enhanced their intraoral intake of 0.5 M NaCl in response to sodium depletion while CeAX rats did not. CeAX rats, however, showed discriminative intake responses to tastes. Like controls, CeAX rats promptly rejected 0.3 mM quinine infusions and ingested 1.0 M sucrose for prolonged periods. In addition, food deprivation enhanced the intraoral intake of a dilute sucrose solution in both CeAX and control rats. Thus, in the CeAX rat some tastes and some internal states modulate intake as they do in intact rats. These results are consistent with the hypothesis that central nucleus of the amygdala damage interferes with the consummatory phase of NaCl intake behaviors.

Administration, Oral↗
PubMed1993

Effects of interrupting an intraoral meal on meal size and meal duration in rats.

Most experiments on satiation do not separate the contribution to meal size of cumulative intake from that of time since meal onset. To assess the relative contributions of temporal and intake factors, the amount consumed of intraorally infused 12.5% glucose solution, delivered at a fixed rate of 1.0 ml/min, was assessed after tests that were interrupted for variable durations (Experiments I and II) beginning at different times within the test meal (Experiment I). Rats' meal size did not vary despite the imposition of single or multiple pauses which interrupted ingestion for as long as 38 min. These results show that, within this paradigm, the duration of the meal varies in service of an intake "goal". Such a defense of meal size requires accurate monitoring of the postingestive load despite its redistribution by continued gastric emptying during the imposed pauses in ingestion.

Animals↗
PubMed1993

Daily caloric intake in intact and chronic decerebrate rats.

Daily caloric intake regulation was studied in chronic supracollicular decerebrate rats with a complete transection of the neural axis at the meso-diencephalic juncture and in intact controls. For 1 week, each rat received 3 intraorally delivered meals per day. They were challenged to maintain their 3-meal daily intake over 1 week in which only 2 meals per day were delivered. Intact rats increased meal size to compensate for the lost opportunity to feed, whereas chronic decerebrate rats did not. Results suggest that, although the caudal brainstem, as previously shown (Grill & Kaplan, 1990), is sufficient to modulate ingestive behavior in taste reactivity and single-meal tests, it is not sufficient to regulate daily caloric intake. Although it is possible that chronic decerebrate rats retain a long-term regulatory competence that is somehow masked under the meal omission paradigm, forebrain-hindbrain interactions appear necessary for the coordination of short- and long-term intake control processes.

Animals↗
PubMed1981

Studies on the sidedness of the human red blood cell membrane: preparation of stable azo-erythrocytes.

Para-diazobenzenesulfonic acid (DBSA), a non-penetrating compound, which reacts with proteins of the external surface of intact cells, was used for the preparation of AZO-erythrocytes. When coupling of p-diazobenzenesulfonic acid to human red blood cells was carried out in phosphate-buffered saline (PBS), the cells lysed within one hour, before the completion of the reaction. Elimination of sodium chloride from the reaction mixture allowed the completion of coupling by prolonging the survival of red blood cells in he diazonium salt from one hour to three hours. The survival of human erythrocytes could be further prolonged to seven hours by carrying out coupling in the presence of cyclic 3',5'-guanosine monophosphate (cGMP). Azo-erythrocytes prepared in the absence of cyclic GMP and washed free of the diazonium salt lysed in phosphate-buffered saline, but remained stable for hours in isosmotic phosphate buffers devoid of sodium chloride ions. Under identical conditions, azo-erythrocytes prepared in the presence of cyclic GMP remained stable for two days and were suited for studies on the functional and structural aspects of red blood cell membrane.

Acetylcholinesterase↗