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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 253 records · Page 14Linked to original sources
PubMed1989

Brain 3-hydroxybutyrate, glutamate, and GABA in a rat model of dietary obesity.

Whole brain concentrations of 3-hydroxybutyrate, glutamate and gamma-aminobutyric acid (GABA) have been measured in two strains of rats with differing susceptibility to obesity. S 5B/Pl rats are resistant to developing obesity when eating a high-fat diet, whereas Osborne-Mendel rats readily develop obesity when eating the same diet. We tested the hypotheses that brain 3-hydroxybutyrate, glutamate and GABA differ between S 5B/Pl rats and Osborne-Mendel rats, and that these substrates/neuroregulators are altered when eating a high-fat diet primarily in S 5B/Pl (resistant) rats. Blood and brain 3-hydroxybutyrate concentrations were higher in S 5B/Pl rats than in Osborne-Mendel rats (p less than 0.05) but diet effects were not significant. Brain glutamate concentration, like 3-hydroxybutyrate, was higher in S 5B/Pl rats than in Osborne-Mendel rats (p less than 0.01) and was not affected by adding fat to the diet. Brain GABA differed only slightly between strains but increased after adding fat to the diet (p less than 0.05) in both strains with a greater increase occurring in S 5B/Pl rats. The brains of S 5B/Pl rats are chronically exposed to higher levels of 3-hydroxybutyrate and glutamate than are those of Osborne-Mendel rats. Thus, 3-hydroxybutyrate is a potential signal in the regulation of body weight. Brain GABA increases with fat feeding, especially in S 5B/Pl rats, suggesting that the ability to adjust to an energy dense diet may be through suppression of food intake by elevated brain GABA.

3-Hydroxybutyric Acid↗
PubMed1989

Effects of food restriction and adrenalectomy in rats with VMH or PVH lesions.

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.

Adipose Tissue, Brown↗
PubMed1989

Effect of a high-fat diet on firing rate of sympathetic nerves innervating brown adipose tissue in anesthetized rats.

Three experiments have examined the effects of ad lib and forced intake of a high-fat diet on sympathetic firing rate to brown adipose tissue. Seven days after beginning of ad lib intake of either a low-fat or high-fat diet, sympathetic activity was not significantly different in either group nor was it significantly different from the values obtained in animals measured at the switch from the chow to a semisynthetic high- or low-fat diet. After 22 days on the semisynthetic diet, however, the sympathetic firing rate of animals eating the high-fat diet had decreased nearly 25% and was significantly lower than the animals maintained on the semisynthetic low-fat diet or animals studied at the transition from the chow to the low-fat diet. In a second experiment animals were tube-fed for 3, 6 or 9 weeks on a high- or low-fat diet. Sympathetic firing rate of the rats eating the low-fat diet was higher at all three times, but the difference decreased with longer feeding. To eliminate differences in food intake, animals were tube-fed a moderate- or high-fat liquid diet three times a day for six days. The 80 kcal/day intake produced a steady weight gain in both groups. Liver weight, retroperitoneal white adipose tissue weight, and interscapular brown adipose tissue weight were all significantly greater in the animals fed the high-fat diet. Sympathetic firing rate, however, was significantly lower in the animals fed the high-fat semisynthetic diet as compared to animals fed the moderate-fat diet. These data show the high-fat diets are associated with a reduction in sympathetic activity to brown adipose tissue.

Adipose Tissue, Brown↗
PubMed1989

Effects of neuropeptide Y on norepinephrine and serotonin metabolism in rat hypothalamus in vivo.

A double-barrelled cannula and microdialysis system were used to inject 100 pmoles of neuropeptide Y (NPY) and to collect from the local microenvironment samples of norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) a metabolite of dopamine. Following the administration of 100 pmoles of NPY into the ventromedial hypothalamus of conscious rats, there was a significant reduction in the local concentration of norepinephrine and an even greater reduction in the concentration of its metabolite, MHPG, as compared to saline-injected controls. The concentration of serotonin and its metabolite 5-HIAA as well as DOPAC were also reduced in the ventromedial hypothalamus following local injection of NPY. When NPY was injected into the lateral hypothalamus and monoamines measured from areas adjacent to the injection of NPY there was a significant increase in norepinephrine release and a significant increase in the concentration of DOPAC. Serotonin was significantly decreased and there was an increase in the ratio of 5-HIAA to serotonin. NPY is known to stimulate food intake when injected into either area. The present data are consistent with the concept that a reduction in concentration of serotonin is involved in the regulation of food intake following injection of NPY.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Acetylation alters the feeding response to MSH and beta-endorphin.

The effects on food intake of the N-acetylation of MSH and beta-endorphin have been examined following their injection into the third ventricle. Desacetyl-MSH and alpha-MSH were injected into fasted rats, and beta-endorphin and N-acetyl-beta-endorphin into fed rats. Desacetyl-MSH had no effect on food intake following ICV injection into food-deprived rats at any dose between 100 and 2500 pmoles. Alpha-MSH, the N-acetylated form of MSH, on the other hand, showed a highly significant inhibition of food intake in food-deprived rats with doses of 100 and 250 pmoles but no effect with the higher doses. With beta-endorphin, there was a dose-related biphasic effect. One hour after injection of beta-endorphin (2500 pmole) food intake was inhibited whereas the lowest dose, 100 pmole, significantly stimulated it. By 3 hours, the 2 lowest doses of beta-endorphin both significantly stimulated food intake, but the highest dose remained inhibitory. By 6 hours all doses of beta-endorphin stimulated food intake compared to the vehicle-treated animals. In contrast, N-acetylation of beta-endorphin eliminated all effects on food intake following injection into the third ventricle. These data suggest that N-acetylation of products formed by the processing of POMC can markedly alter their biological properties.

Acetylation↗
PubMed1989

Nutrient balance and obesity: an approach to control of food intake in humans.

This article has examined the regulated systems that control nutrient balance. From this analysis, the following conclusions may be suggested: 1. Each nutrient is regulated separately in a feedback system. 2. The control of glucose is regulated by the size of the glycogen stores; the size of the fat depots, by the rate of hepatic fatty acid oxidation; and protein, by the size of the protein depots. 3. Obesity can occur as a result of hyperphagia or from repartitioning the deposition of nutrients. In either case, there is a relative or absolute reduction in the activity of the sympathetic nervous system, requiring adequate levels of circulating corticosteroids.

Body Weight↗
PubMed1989

Classification and evaluation of the obesities.

Obesity is a condition of multifactorial etiology that can be associated with important health and functional consequences. Suggestions for the proper evaluation of obese patients have been presented along with brief descriptions of the rationales for their use. The evaluation protocol has been summarized in two algorithms to aid in the performance of a complete and organized work-up.

Adipose Tissue↗
PubMed1989

Drug treatment of obesity.

Use of drugs for the treatment of obesity is regarded more skeptically than drug use in other chronic disease; this view, however, may be inappropriate. Anorexiant drugs, the major class of drugs currently available for treating obesity, differ in several important ways, including whether they act on noradrenergic or serotonergic systems and in their potential for abuse. New approaches to drug treatment of obesity include thermogenic agents and drugs acting on the digestive system and hormones.

Humans↗
PubMed1989

Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system.

The basic hypothesis of this review is that studies on models of experimental obesity can provide insight into the control systems regulating body nutrient stores in humans. In this homeostatic or feedback approach to analysis of the nutrient control system, we have examined the afferent feedback signals, the central controller, and the efferent control elements regulating the controlled system of nutrient intake, storage, and oxidation. The mechanisms involved in the beginning and ending of single meals must clearly be related to the long-term changes in fat stores, although this relationship is far from clear. Changes in total nutrient storage in adipose tissue can arise as a consequence of changes in the quantity of nutrients ingested in one form or another or a decrease in the utilization of the ingested nutrients. A change in energy intake can be effected by increased size of individual meals, increased number of meals in a 24-hour period, or a combination of these events. Similarly, a decrease in utilization of these nutrients can develop through changes in resting metabolic energy expenditure which are associated with one of more of the biological cycles such as protein metabolism, triglyceride for glycogen synthesis and breakdown, or maintenance of ionic gradients for Na+ + K+ across cell walls. In addition, differences in energy expenditure related to the thermogenesis of eating or to the level of physical activity may account for differences in nutrient utilization.

Animals↗
PubMed1989

Adrenalectomy in genetically obese ob/ob and db/db mice increases the proton conductance pathway.

Adrenalectomy (ADX) prevents the excessive weight gain in the genetically obese ob/ob and db/db mice. To test the possibility that this results from increased energy expenditure due to increased thermogenesis in brown adipose tissue (BAT), we measured GDP binding to mitochondria from interscapular brown adipose tissue (BAT) in db/db and ob/ob mice and their lean controls after adrenalectomy, with and without corticosterone replacement. Both the vehicle treated and corticosterone treated db/db and ob/ob mice had lower body weights than the sham-operated mice GDP binding to mitochondria from IBAT was significantly lower in both the db/db and ob/ob mice than in their lean controls. Adrenalectomy significantly increased GDP binding in all mice compared to the respective sham-operated mice, but, the percentage increase was always greater in the db/db and ob/ob mice. Corticosterone treatment of adrenalectomized db/db, ob/ob or lean mice lowered GDP binding to sham levels. Our data confirm previous findings that adrenalectomy results in increased GDP binding to mitochondria from IBAT. Injections of corticosterone into adrenalectomized mice results in a decrease in GDP binding to values which are similar to values in sham-operated mice. Thus adrenalectomy may inhibit the development of obesity by increasing the thermic activity in IBAT.

Adipose Tissue↗
PubMed1989

Effect of obesity on bioelectrical impedance.

The purpose of this study was to validate the use of bioelectrical impedance in assessing human body composition and to explore the use of this technique in obesity. Eighty-seven adults varying widely in body composition (range: 8.8-59.0% body fat) underwent measurement of bioelectrical impedance and underwater weighing (density). Fat-free mass determined from density (FFMd) was compared with FFM estimated from bioelectric impedance according to previously published regression equations. Correlation coefficients were high at all levels of body fat (0.94-0.99) but impedance equations overestimated FFM compared with FFMd in subjects greater than 42% body fat. This effect was greatest in subjects greater than 48% body fat and a regression equation was derived for determination of FFM for these subjects. These data confirm the excellent agreement between body composition determined from bioelectrical impedance and density but suggest that caution should be used in applying existing regression equations to very obese subjects.

Adult↗
PubMed1989

1989 McCollum Award lecture. Genetic and hypothalamic mechanisms for obesity--finding the needle in the haystack.

The elements of a feedback system for regulating body fat stores consists of an afferent limb providing feedback signals to the central controller in the brain, which integrates information from the sensory and autonomic nervous systems with signals from the internal milieu and modulates ingestive behavior and thermogenic components of the adrenergic nervous system. The search for defective mechanisms that produce obesity has utilized animals with genetic, hypothalamic, and dietary types of obesity. In all three cases, obesity is associated with an absolute or relative decrease in the activity of the sympathetic nervous system. Experimental situations associated with reduced activity of the sympathetic nervous system are generally accompanied by increased food intake and vice versa. Hypothalamic obesity results from damage to the ventromedial hypothalamus, which disrupts modulation of the autonomic nervous system by nutrient and hormonal signals. Recessively inherited obesity may result from failure to modulate the steroid-receptor complex interaction with the promoter region of the genome. Impaired acetylation of melanocyte-stimulating hormone (MSH) may be involved in the development of obesity in the obese yellow mouse. In all cases adrenalectomy arrests the progression or reverses the obesity. These findings further strengthen the autonomic and endocrine hypothesis for obesity.

Animals↗
PubMed1989

Adrenalectomy and response to corticosterone and MSH in the genetically obese yellow mouse.

Animals with the viable yellow (Avy/a) gene and their corresponding lean control black mice (a/a) were adrenalectomized or sham adrenalectomized, and changes in body weight, body composition, corticosterone, and GDP-binding to mitochondria isolated from interscapular brown adipose tissue (IBAT) were measured. Adrenalectomy slowed the weight gain of both the yellow obese mice and the black lean mice, but the reduction was greater in the yellow mice. Food intake was significantly reduced in the yellow mice. Adrenalectomy in the yellow mouse was associated with an increase in lean mass and a significant decrease in weights of fat depots. Blood glucose concentrations of the adrenalectomized yellow mice were reduced to levels similar to those of lean mice, but insulin levels, although lower than sham-adrenalectomized yellow mice, remained significantly higher than in lean animals. GDP binding to IBAT mitochondria increased after adrenalectomy in both phenotypes to values that were similar. Corticosterone replacement in adrenalectomized yellow mice produced a dose-dependent increase in body weight that was associated with a decrease in muscle weight and an increase in adipose tissue weight. Both desacetyl-melanocyte-stimulating hormone (MSH) and alpha-MSH interacted with corticosterone to increase body weight gain of adrenalectomized yellow mice. Desacetyl-MSH was more effective than alpha-MSH on increasing adipose tissue and liver weights. The effects of desacetyl-MSH on food intake, weight gain, and tissue weights were independent of the adrenal gland or of corticosterone.

Adipose Tissue, Brown↗
PubMed1989

Effects of intraventricular infusion of corticotropin-releasing factor on VMH-lesioned obese rats.

Corticotropin-releasing factor (CRF) has been administered into the third ventricle of sham-operated and ventromedial hypothalamic (VMH)-lesioned rats in acute and chronic experiments. After a single 5-microgram injection of CRF, there was an acute reduction of food intake in both sham-operated and VMH-lesioned rats that persisted for 3 h. The effect was still present in the VMH-lesioned rats between 3 and 6 h but had dissipated in the sham-operated controls. Guanosine 5'-diphosphate (GDP) binding to mitochondria from interscapular brown adipose tissue was used as an index of thermogenic activity in this tissue. In 21-h food-deprived rats, GDP binding was significantly lower in VMH-lesioned than in sham-operated animals. Although the mean increase in sham-operated animals was increased, this was not significantly different from saline-injected controls. In the VMH-lesioned rats, however, CRF acutely increased GDP binding to values not different than those of the sham-operated controls. Serum corticosterone was significantly lower in the VMH-lesioned rats, but both groups showed a significant stimulation by CRF during a 7-day infusion of CRF (4.8 micrograms/day) into the third ventricle. Food intake was significantly depressed in the VMH-lesioned animals that received CRF, from values of 35 g/day to approximately 25 g/day. Body weight showed a slow steady decrease, having fallen by nearly 15 g at the end of the 7-day infusion period. In contrast the mean value in the VMH-lesioned controls had significantly higher in CRF-infused animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1989

Effects of 2-deoxy-D-glucose on sympathetic nerve activity to interscapular brown adipose tissue.

The effects on firing rate of sympathetic nerves to interscapular brown adipose tissue were measured after induction of intracellular glycopenia by peripheral or central administration of 2-deoxy-D-glucose (2-DG). Injection of 2-DG (250 mg/kg body wt) into the jugular vein rapidly suppressed the sympathetic activity, which declined 84% within 10 min after the injection. This suppression persisted for at least 40 min. Hyperglycemia did not affect the sympathetic activity but partially inhibited the suppressive effect of 2-DG injection. Acute vagotomy failed to block the suppressive effect of 2-DG. Injection of 2-DG (2.5 mg/rat) into the third cerebral ventricle suppressed the sympathetic activity. This suppression was followed by gradual recovery. Saline injection did not affect the sympathetic activity. We conclude that cellular glycopenia induced by injecting 2-DG peripherally or into the third cerebral ventricle suppresses the sympathetic activity to brown adipose tissue. The results are consistent with the hypothesis that an acute energy shortage decreases the thermogenesis in interscapular brown adipose tissue by suppressing sympathetic neural activation of this tissue.

Adipose Tissue, Brown↗
PubMed1989

Lateral hypothalamic injection of 2-deoxy-D-glucose suppresses sympathetic activity.

To investigate the effects of glucoprivation on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), 2-deoxy-D-glucose (2-DG) was injected into the third cerebral ventricle (icv), lateral hypothalamic area (LHA), and ventromedial hypothalamic nucleus (VMN) of rats. The multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically. The icv injection of high and low doses of 2-DG (5.0 and 2.5 mg/rat) suppressed sympathetic nerve activity by 76.9 and 49.8% respectively, 30 min after injection compared with preinjected base line. After the low dose of 2-DG, there was a gradual recovery, but after the high dose recovery did not occur. The unilateral microinjection of 2-DG (0.25 mg/rat) into the LHA induced a similar suppression of sympathetic nerve activity to that observed after icv injection of 10 times as much 2-DG (-25.3%). The injection of vehicle or sucrose into the LHA did not suppress sympathetic nerve activity. The microinjection into the VMN either unilaterally or bilaterally did not suppress sympathetic nerve activity to IBAT. We conclude that the LHA but not the VMH is one site of action of 2-DG. The data are consistent with the hypothesis that the brain senses glucoprivation in the LHA and reduces sympathetic drive to thermogenic tissues such as IBAT.

Adipose Tissue, Brown↗
PubMed1989

Effects of dexamethasone on glucose transport by skeletal muscles of obese (ob/ob) mice.

Adrenalectomy normalized basal and insulin-stimulated glucose transport in the perfused hindquarter of the obese (ob/ob) mouse. Dexamethasone treatment of adrenalectomized obese mice for 9 days significantly reduced both the basal and insulin-stimulated uptake of (3H)-2-deoxy-D-glucose in hindlimbs of adrenalectomized mice to levels similar to those of intact ob/ob mice. Five hours after injection of dexamethasone in vivo and following 5 hours of perfusion in vitro there was a 10 percent reduction in basal 2-deoxy-D-glucose uptake in both groups. In muscles perfused with dexamethasone in vitro, the stimulation of 2-deoxy-D-glucose uptake by insulin was greater than in those muscles perfused with vehicle alone. Five hours of treatment in vivo also resulted in a significant increase in liver tyrosine aminotransferase activity, and a decrease in muscle glycogen synthetase activity ratio. These data suggest that the effect of glucocorticoids on lowering glucose transport in the skeletal muscle of obese ob/ob mice is a direct one.

Adrenalectomy↗