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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 181 records · Page 10Linked to original sources
PubMed1993

The nutrient balance hypothesis: peptides, sympathetic activity, and food intake.

Food intake can be increased or decreased after either central or peripheral administration of peptides. Galanin, neuropeptide Y, opioid peptides, growth hormone releasing hormone and desacetyl-MSH increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin releasing hormone, neurotensin, bombesin, enterostatin, cyclo-his-pro and thyrotropin-releasing hormone reduce food intake. A number of these peptides also affect the activity of the sympathetic nervous system. The peptides which have been tested have a reciprocal effect on food intake and sympathetic activity. Opioids, NPY and GHRH, which increase food intake, decrease sympathetic activity. Conversely, peptides which reduce food intake, increase sympathetic activity, with glucagon, cholecystokinin, corticotropin releasing hormone, calcitonin, neurotensin and bombesin being examples, Several of these peptides also affect the intake of specific nutrients. Insulin reduces food intake in animals fed a high carbohydrate diet, but not when fed a high fat diet. Neuropeptide Y increases carbohydrate intake. Galanin and opioid peptides increase fat intake. Enterostatin and cyclo-His-Pro, on the other hand reduce fat intake. Glucagon decreases protein intake. The effect of peptides on the intake of specific nutrients suggests that peptides may work in part by modulating basic feeding mechanisms to lead to the selection of specific nutrients from the diet. This hypothesis might be called a nutrient specific model of peptide-induced food intake.

Animals↗
PubMed1993

Sympathetic nerve activity after discrete hypothalamic injections of L-glutamate.

In these experiments L-glutamate, an amino acid which stimulates neuronal discharge, was microinjected into several hypothalamic nuclei and the resultant changes in electrical firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) were measured. Three patterns of response were seen. A single large stimulatory response was seen when L-glutamate was microinjected into the ventromedial hypothalamus (VMH). Microinjection of L-glutamate into the paraventricular nucleus (PVN) produced a predominantly stimulatory response which was of smaller magnitude than the VMN. However in three animals L-glutamate in the PVN decreased firing rate and in one animal a biphasic response was observed. The second pattern was a decrease in sympathetic activity to IBAT which was the predominant pattern following injection of L-glutamate into the dorsomedial hypothalamus (DMH). However, a biphasic pattern was also observed. Injection of L-glutamate into the lateral hypothalamic area (LHA) produced 3 patterns of response; an increase, a decrease; or a biphasic response in nearly equal numbers of animals. The predominant response to L-glutamate in the preoptic area (POA) was biphasic. These data are consistent with the hypothesis that the VMH is the predominant stimulatory site for activation of the sympathetic nervous system to IBAT in the rat. The DMH and LHA appear to be the predominant inhibitory areas.

Adipose Tissue, Brown↗
PubMed1993

Adrenalectomy and castration in the genetically obese (ob/ob) mouse.

The present studies have tested the hypothesis that adrenalectomy could modify the phenotypic expression of genetic obesity by examining the effects of adrenalectomy on the function of the gonadal system in lean and ob/ob mice. Corticosterone concentrations were undetectable in the adrenalectomized animals. Adrenalectomy significantly slowed the weight gain of obese mice in comparison to sham-adrenalectomized controls. Gonadectomy had no independent effect on weight gain. The testes, prostate, and seminal vesicles in the ob/ob mice were significantly smaller than in the lean animals. Castration lowered the weights of the prostate and seminal vesicles in the lean mice to weights close to those observed in the castrated ob/ob mice. Castration significantly increased the concentrations of LH and FSH in both ob/ob and lean mice, but the absolute concentrations were higher in the lean mice in both conditions. Adrenalectomy per se had no effect on the concentration of LH, FSH, or testosterone or on the weights of the prostate or seminal vesicles. These data indicate that adrenalectomy has no effect on the physiologic control of the reproductive system in genetically obese mice, and are consistent with the hypothesis that the defect in the ob/ob mouse is a modulator of steroid action which over expresses glucocorticoid effects and under expresses gonadal steroid effects.

Adrenal Glands↗
PubMed1993

Insulin secretion in hypothalamic obesity: diurnal variation and the effect of naloxone.

This paper has tested the hypothesis that patients with hypothalamic obesity have altered mechanisms controlling insulin secretion when compared to obese patients without hypothalamic injury. Fasting glucose and insulin values were significantly higher in the morning than in the afternoon in the six control obese patients, but there was no diurnal difference in the six patients with hypothalamic obesity (n=6). The control obese subjects showed a diurnal variation in glucose-stimulated insulin secretion, whereas the patients with hypothalamic obesity did not, suggesting that hypothalamic injury had destroyed diurnal rhythms. Naloxone, an opioid antagonist, acutely suppressed fasting insulin in the six patients with essential obesity but had little effect on fasting insulin in the three patients with hypothalamic obesity or in five normal-weight controls. Naloxone increased insulin sensitivity in the obese control patients, but did not affect either insulin secretion or insulin sensitivity in patients with hypothalamic obesity or in normal weight subjects. Our results support the conclusion that hypothalamic obesity disrupts diurnal rhythms, with the suggestion that opioid peptides affect insulin secretion differently in patients with essential obesity as compared to normal weight subjects or those with hypothalamic obesity.

Adolescent↗
PubMed1993

Effect of enterostatin on the feeding responses to galanin and NPY.

We have investigated the possibility that enterostatin may inhibit the intake of dietary fat by inhibiting either galanin or NPY-induced feeding pathways. Rats, adapted to either high fat (HF) or low fat-high carbohydrate (HC) diets and fitted with third ventricular cannulas were used to study the effects of intracerebroventricular (i.c.v.) enterostatin on i.c.v. NPY and galanin induced feeding responses in satiated rats. An equimolar dose of enterostatin (0.1 nmoles) inhibited, while a tenfold excess of enterostatin abolished the feeding response to galanin in rats adapted to a HF diet. The galanin stimulation of food intake was reduced in rats adapted to the HC diet and this response was less sensitive to inhibition by enterostatin. Enterostatin had no inhibitory effects on NPY-induced feeding in rats adapted to the HC diet and only a small inhibitory effect, at tenfold molar excess, in rats adapted to the HF diet. The ability of enterostatin to bind to galanin or NPY Y-1 receptors was investigated in ligand binding studies. Enterostatin failed to displace 125I-galanin or 125I-PYY from specific binding sites in rat forebrain homogenates or SK-N-MC cells respectively. The data provide support for the hypothesis that enterostatin specifically inhibits a galanin-responsive fat intake system, but indicate that this effect is not modulated by direct interaction with either galanin or NPY-Y1 receptors.

Analysis of Variance↗
PubMed1993

Chronic effects of intracerebral ventricular enterostatin in Osborne-Mendel rats fed a high-fat diet.

Enterostatin, a pentapeptide found in the procolipase molecule of the pancreas, has been infused chronically into the lateral ventricle of Osborne-Mendel rats for 11 days. Treatment with enterostatin acutely lowered food intake more in the treated animals than in the vehicle-treated controls. Weight gain and serum insulin were significantly reduced by enterostatin. Corticosterone was significantly increased in rats receiving chronic infusions of enterostatin into the lateral ventricle and was also increased following an acute ICV injection of enterostatin. CRH antagonist did not block the acute feeding response to enterostatin in Sprague-Dawley rats. The elevation of corticosterone during chronic infusion of enterostatin reduced the level of hepatic glucocorticoid receptor as measured by Western blot. We conclude that body weight gain of OM rats is reduced by centrally administered enterostatin, and that the acute effects of enterostatin on food intake are not mediated through stimulation of CRH secretion.

Animals↗
PubMed1993

The peptide enterostatin may produce early satiety.

The time course of feeding, grooming, exploration, and sleeping behaviors has been measured following treatment with enterostatin, the signal pentapeptide from procolipase. The peptide was injected intraperitoneally prior to presenting food, and the frequency of feeding and grooming activity, drinking, and rest or sleeping were observed at 10-s intervals for 60 min. Enterostatin did not delay the onset of feeding but shortened the time spent eating compared to saline injected controls. Conversely, grooming activity appeared earlier following enterostatin, activity was reduced, and resting behavior occurred earlier with this peptide. There were no changes in the drinking behavior. For the first hour following enterostatin, eating represented 20.8% of the time, grooming 9.2%, activity 18.3%, and rest or sleep 47.2%, with drinking making up the other 4.4%. In contrast, saline-injected animals ate for 27.1% of the time, groomed for 12.4%, were active 28.5% of the time, had sleep or rest time equal to 27.9%, and drank for 4.1% of the time. In fasted animals, the onset of grooming, the decrease in activity, and the increase in time sleeping occurred earlier than with saline. These studies support the concept that enterostatin decreases food intake by producing early satiety.

Animals↗
PubMed1993

d-fenfluramine in a rat model of dietary fat-induced obesity.

d-Fenfluramine is an appetite suppressant drug that acts by releasing serotonin from axon terminals and inhibiting its reuptake. S 5B/P1 rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to ad lib feeding of either a low- or high-fat diet. d-Fenfluramine (10 mg/kg, IP) was injected daily for 12 days. Other than a slightly greater suppression of food intake in Osborne-Mendel rats, there was little difference in response to d-fenfluramine between S 5B/P1 and Osborne-Mendel rats eating the low-fat diet. However, in Osborne-Mendel rats d-fenfluramine completely abolished the excess food intake and weight gain associated with the high-fat diet. Purine nucleotide (GDP) binding on day 13 was higher in S 5B/P1 rats than in Osborne-Mendel rats and was increased by d-fenfluramine in animals of both strains eating the low-fat diet. The high-fat diet increased GDP binding only in S 5B/P1 rats and blocked the fenfluramine-induced increase in GDP binding in both strains. We speculate that d-fenfluramine blocks a feeding reward system stimulated by the high-fat diet.

Animals↗
PubMed1993

Improved yield of obese rats using a double coordinate system to locate the ventromedial or paraventricular nucleus.

This article describes a highly efficient method for making VMH and PVN-lesioned obese rats by using a newly developed coordinate system. In previous methods, the coordinates for creating VMH and PVN lesions were determined from single point, either the interaural line or the bregma. Because skull size varies, the use of two reference points resulted in greater consistency. We therefore developed a system for making VMH- and PVN-lesioned obese rats using both the interaural line and the bregma. With this new double coordinate system the success rate for producing obese rats varied from 52% to 92% for VMH lesions and from 36% to 61% for PVN lesions.

Animals↗
PubMed1993

Food intake, sympathetic activity, and adrenal steroids.

Food Intake is reciprocally related to the activity of sympathetic nerves to brown adipose tissue. This reciprocal or feedback relation is shown for hypothalamic lesions, drugs, and many peptides. These peptides also modulate intake of specific nutrients. Galanin and opioids increase fat intake, whereas enterostatin decreases fat intake. NPY increases carbohydrate intake and growth hormone releasing hormone decreases protein intake. The activity of the sympathetic nervous system is low in obesity and adrenalectomy reverses this decrease in sympathetic activity and reverses or stops the progression of obesity. One mechanism for this effect of adrenal steroids is through a transacting substance which is involved in steroid actions and the production of obesity.

Adrenal Glands↗
PubMed1993

Effect of beta-endorphin on sympathetic nerve activity to interscapular brown adipose tissue.

beta-Endorphin was injected into the third cerebroventricle to investigate its effects on sympathetic nerve activity to interscapular brown adipose tissue (IBAT) in rats. Multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically in anesthetized rats. The intracerebroventricular injection of beta-endorphin (125, 250, and 500 pmol/rat in 10 microliters) suppressed sympathetic nerve activity in a dose-related fashion (-23.9 +/- 20.4, -38.7 +/- 7.1, and -66.7 +/- 7.6% 30 min after injection) compared with preinjection baseline. N-acetyl-beta-endorphin (250 pmol) had no effect on sympathetic nerve activity to IBAT. The intraperitoneal injection of naloxone (5.0 mg/rat) did not affect sympathetic nerve activity, but preinjection of naloxone inhibited the suppressive effect of intracerebroventricular injection of beta-endorphin (250 pmol). We conclude that the intracerebroventricular administration of beta-endorphin suppressed the sympathetic nerve activity to IBAT through opioid receptors. The results of this experiment are consistent with the hypothesis that beta-endorphin has a reciprocal effect on food intake and the sympathetic nervous system.

Adipose Tissue, Brown↗