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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 289 records · Page 16Linked to original sources
PubMed1987

Brain uptake of ketones in rats with differing susceptibility to dietary obesity.

The effect of a low- and high-fat diet on the transport of 3-hydroxybutyrate and glucose across the blood brain barrier has been measured in two strains of animals that have a marked difference in the degree of obesity that develops when they eat a high fat diet. The S 5B/Pl rats are resistant to dietary obesity whereas the Osborne-Mendel rats readily develop obesity when eating a high-fat diet. The transport of 3-hydroxybutyrate and glucose across the blood-brain barrier was measured as the ratio of radioactive compound (3-hydroxybutyrate or glucose) to radioactively labeled water by the technique of Oldendorf. The uptake of 3-hydroxybutyrate was significantly higher in the S 5B/Pl rats than in the Osborne-Mendel rats when they were eating either the low-fat diet or the high-fat diet. In addition, there was a significant increase in the transport of 3-hydroxybutyrate in the animals of both strains when eating the high-fat diet as compared to the low-fat diet. However, there was no difference in the transport of glucose between the two strains of rats whether they ate a low-fat or high-fat diet. These data are consistent with the hypothesis that resistance to dietary obesity is associated with increased transport of 3-hydroxybutyrate across the blood-brain barrier.

3-Hydroxybutyric Acid↗
PubMed1987

Corticosterone inhibition of the intracerebroventricular effect of 2-deoxy-D-glucose on brown adipose tissue thermogenesis.

The effects on food intake, blood glucose and the binding of guanosine 5-diphosphate (GDP) to mitochondria from interscapular brown adipose tissue (IBAT) were examined following the injection of 2-deoxy-D-glucose (2-DOG) into the third ventricle of the brain. Microinjections of 2-DOG increased food intake and blood glucose within 30 to 60 min, but binding of GDP to mitochondria from IBAT, on the other hand, was reduced. The order of sensitivity to 2-DOG was IBAT--feeding--hyperglycemia. Implantation of a 50 mg pellet of corticosterone inhibited the stimulatory effect of 2-DOG on feeding and hyperglycemia and prevented the inhibition of GDP binding to mitochondria from IBAT. These data are consistent with the hypothesis that glucocorticoid may inhibit glucose metabolism at multiple sites in the hypothalamus.

Adipose Tissue, Brown↗
PubMed1987

The effect of intrahypothalamic injections of glucose on sympathetic efferent firing rate.

Electrical stimulation of the ventromedial hypothalamus of anesthetized rats, produced an increase in temperature of brown adipose tissue. The magnitude of increase in temperature was linearly related to the frequency (Hz) of electrical stimulation of the hypothalamus. Microinjection of glucose into the ventromedial hypothalamus produced a dose-dependent increase in firing rate of the sympathetic nerves to brown adipose tissue, whereas comparable volumes of physiological saline had no effect. Destruction of neurons in the ventromedial hypothalamus with injections of kainic acid completely blocked the stimulatory effect of glucose on the firing rate of nerves to the brown adipose tissue. These studies support the hypothesis that glucose sensitive neurons in the ventromedial hypothalamus can directly modulate sympathetic nerves supplying brown adipose tissue.

Action Potentials↗
PubMed1987

Adrenalectomy and steroid treatment in obese (ob/ob) and diabetic (db/db) mice.

Adrenalectomy in young obese (ob/ob) and the diabetic (db/db) mouse slowed body weight gain. Treatment of adrenalectomized ob/ob mice with cortisone or deoxycorticosterone acetate (DOCA) significantly increased weight gain in a dose-related manner. Cortisone had no effect on weight gain on lean mice and treatment with dehydroepiandrosterone sulfate was without effect on either ob/ob or lean mice. The increment in body weight of adrenalectomized ob/ob mice treated with corticosterone and DOCA was associated with an increase in body weight and an increase in food intake. When adrenalectomy was performed at twenty-three days of age (five days before weaning), animals carrying the (db/db) genotype remained lighter than their normal littermates. These data document the importance of the adrenal gland and its steroids for the development and maintenance of many features of the obese or diabetes mouse.

Adrenal Glands↗
PubMed1987

Intrahypothalamic injection of insulin decreases firing rate of sympathetic nerves.

Injection of picomolar quantities of insulin into the ventromedial hypothalamus of rats significantly reduced the firing rate of sympathetic nerves that supply interscapular brown adipose tissue. The minimal firing rate was reached in 2 min, and the effect was gone within 4 min. The effect of insulin was dose-related and did not occur when comparable volumes of physiological saline were injected into the ventromedial hypothalamus. Destruction of neurons in the ventromedial hypothalamus by injection of kainic acid abolished the inhibitory effects of insulin. These data suggest that insulin may play a role in modulating the sympathetic firing rate to thermogenically important tissues.

Adipose Tissue↗
PubMed1987

Overweight is risking fate. Definition, classification, prevalence, and risks.

In this paper I have defined obesity and indicated its prevalence, as well as its risks. Body fat and its relation to other body components can be quantitated in many ways. From a practical point of view, the use of body mass or Quetelet index, defined as the ratio of weight (kg) divided by the square of the height (m2) is the most useful. Overweight is defined as a BMI of 25 to 30 kg/m2 and obesity as a BMI above 30 kg/m2. The WHR can provide additional information about the risk of obesity. Using BMI, the prevalence of overweight in the English-speaking countries of Australia, Great Britain, and the United States is almost identical at 24% of women and 31 to 34% of men. In the obese category, there are more Americans (12%) than in the other two countries (6-8%). There is a U-shaped relationship between weight and risk of death. When body weight is increased 20% above average, the extra mortality rises to 20% for men and 10% for women. This extra mortality is associated with an increased death rate from heart disease, hypertension, diabetes mellitus, digestive diseases, and cancer. In addition to an increased risk of death, overweight individuals demand more from their heart, lungs, and musculoskeletal and digestive systems.

Adult↗
PubMed1987

Diet, lighting, and food intake affect norepinephrine turnover in dietary obesity.

The effects of dietary fat content, lighting cycle, and feeding time on norepinephrine turnover in interscapular brown adipose tissue, heart, and pancreas, and on blood 3-hydroxybutyrate, serum glucose, insulin, and corticosterone have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to dietary obesity, have a more rapid turnover of norepinephrine in interscapular brown adipose tissue and heart and a greater increase in the concentration of norepinephrine in brown fat when eating a high-fat diet than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. Light cycle and feeding schedule are important modulators of sympathetic activity in heart and pancreas but not in brown fat. Rats of the resistant strain also have higher blood 3-hydroxybutyrate concentrations and lower insulin and corticosterone levels than do rats of the susceptible strain. A high-fat diet increases 3-hydroxybutyrate concentrations and reduces insulin levels in both strains. These studies show, in rats eating a high-fat diet, that differences in norepinephrine turnover, particularly in brown adipose tissue, may play an important role in whether dietary obesity develops and in the manifestations of resistance to this phenomenon observed in the S 5B/Pl rat.

Animals↗
PubMed1987

Dynamic and static phases of obesity following lesions in PVN and VMH.

The effect of electrolytic lesions in the ventromedial hypothalamus (VMH) and the paraventricular nucleus (PVN) has been compared during both the dynamic and static phase of weight gain. Hyperphagia and weight gain were greater in the VMH-lesioned rats than in the PVN-lesioned rats. Food intake increased at night after both lesions but increased in the daytime only in VMH-lesioned rats. During the dynamic phase of rapid weight gain, the diurnal pattern of corticosterone was blunted to a similar degree in both lesioned groups. The morning insulin concentrations were higher in both lesioned groups than in the sham-operated controls, but in the static phase only the VMH-lesioned rats had higher insulin levels. In the afternoon the insulin was higher in the VMH-lesioned rats than in either the sham-operated or PVN-lesioned rats. In the dynamic phase the weight of interscapular brown adipose tissue was significantly increased in the VMH-lesioned rats, but the specific GDP binding was depressed both in the morning and afternoon when compared with either the sham-operated or PVN-lesioned groups. In both the dynamic and static phases GDP binding was similar in sham-operated and PVN-lesioned animals. The differences in concentration of corticosterone in morning and afternoon were smaller in the lesioned groups than in the controls. These data are consistent with the hypothesis that animals with PVN lesions do not show the disturbances in food intake or in the autonomic nervous system that characterize the VMH-lesioned rats.

Adipose Tissue, Brown↗
PubMed1987

Brown fat thermogenesis in a rat model of dietary obesity.

The effects of chronic feeding of a high-fat diet or a cafeteria-type diet on weight gain and thermogenesis in brown adipose tissue as measured by the binding of a purine nucleotide (guanosine 5'-diphosphate, GDP) to mitochondria of brown adipose tissue have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to developing obesity when eating a high-fat diet or drinking sucrose solutions, have greater specific GDP binding in interscapular brown adipose tissue (IBAT) than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. A high-fat diet, fed isoenergetically to the low-fat diet, did not increase the growth of IBAT and decreased specific GDP binding in both strains. Feeding a cafeteria diet resulted in obesity and increased mass and protein content of the IBAT in both strains of rats. However, specific GDP binding increased in response to cafeteria feeding only in the Osborne-Mendel rats. These studies show that thermogenesis, as measured by GDP binding to mitochondria in brown adipose tissue, is suppressed by both isoenergetic and ad libitum feeding of a high-fat diet. The higher basal GDP binding in the brown fat of the S 5B/Pl rats suggests that higher thermogenesis of this tissue contributes to the resistance of this strain to fat-induced obesity. The inability of S 5B/Pl rats to further increase thermogenesis when eating a cafeteria diet may contribute to their becoming obese.

Adipose Tissue, Brown↗
PubMed1987

Effects of feeding behavior of rats of a cryptic peptide from the C-terminal end on prepro-growth hormone-releasing factor.

An amidated peptide derived from cleavage of the C-terminal of prepro-GRF [prepro-GRF-(78-107)NH2] and designated CTPG or anorectin was injected ip and into the third ventricle of rats, and food intake and body weight were measured. An acute injection of 0.2, 0.5, or 1.0 microgram CTPG (anorectin; 60, 150, or 300 pmol) into the third ventricle produced a significant dose-related reduction in food intake in the hungry rat during the 12-h dark period. Water intake was suppressed 30% by 1.0 microgram (300 pmol), but the lower doses had no effect. The highest dose (1 microgram or 300 pmol) produced a small rise in glucose concentration 5 min after injection into the third ventricle, which returned to the control value by 15 min. Anorectin increased the sympathetic efferent firing rate 3, 6, and 24 h after a single injection. Intraperitoneal injection of 2.0, 5.0, and 20 micrograms, however, had no significant effect on food or water intake. Chronic infusion into the third ventricle at a rate of 50 ng/h for 7 days produced a persistent reduction in food intake and a steady fall in body weight. The chronically infused rats had a significantly higher level of sympathetic activity, as measured by the firing rate of sympathetic nerves innervating the interscapular brown adipose tissue. These studies raise the possibility that anorectin released during processing of GRF might be involved in the modulation of feeding behavior.

Animals↗
PubMed1987

Regional fat loss from the thigh in obese women after adrenergic modulation.

Beta-adrenergic stimulation and alpha 2-adrenergic inhibition increase lipolysis from fat cells. Twenty-eight obese women were placed on a calorie-restricted diet and one of five treatments was applied to one thigh three to five times per week for four weeks: (1) isoproterenol injections; (2) cream containing colforsin (forskolin), aminophylline, and yohimbine; (3) yohimbine cream; (4) colforsin cream; or (5) aminophylline cream. The opposite thigh was treated with a placebo (injection or cream). The treated thighs lost significantly more girth after treatment, both by injection and by cream. No adverse reactions were attributable to either the cream or the injections. It is concluded that local fat reduction from the thigh can be safely accomplished.

Adipose Tissue↗
PubMed1987

Nutrient balance: new insights into obesity.

This overview of nutrient balance suggests the following general conclusions. Nutrient balance is in part regulated by the two limbs of the autonomic nervous system. Hypothalamic and genetic obesity are associated with lower levels of sympathetic activity. Conversely the reduced weight of animals with lateral hypothalamic lesions is associated with increased sympathetic activity. Thus the activity of the sympathetic nervous system appears to be inversely related to energy stores. The levels of hormones such as insulin, adrenal steroids, gonadal steroids and growth hormone play an important role in modulating nutrient intake and storage. The data seem to fit the hypothesis that nutrient stores are regulated systems with afferent feedback systems acting on a central controller which regulates intake, storage and metabolism of nutrients through modulation of the autonomic nervous system and motor control of food seeking.

Humans↗
PubMed1986

Effect of ciglitazone on glucose uptake and insulin sensitivity in skeletal muscle of the obese (ob/ob) mouse: distinct insulin and glucocorticoid effects.

The oral hypoglycemic agent, ciglitazone, (5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione), was fed for nine days to genetically obese (ob/ob) mice aged 5 to 6 weeks. This treatment resulted in a lowering of plasma glucose and circulating insulin levels, but did not cause a fall in plasma corticosterone levels. Basal 2-deoxy-D-glucose uptake by the perfused hindquarters of ob/ob mice was unchanged by ciglitazone feeding. In the presence of 0.1 mU/mL insulin in the perfusion medium, there was a significant increase in the uptake rate of 2-deoxy-D-glucose by the skeletal muscle of ciglitazone-treated ob/ob mice, while there was no insulin effect in untreated ob/ob mice. Insulin at a concentration of 1 mU/mL caused a further stimulation of 2-deoxy-D-glucose transport. However, this response was significantly lower than the maximal stimulation in lean mice. Ciglitazone feeding did not have any effect on [5-3H]-glucose metabolism by the perfused muscle which remained subnormal, suggesting that the posttransport metabolism of glucose was limited by substrate availability. In the perfused mouse liver, net [14C]-glucose production from [14C]-lactate was unchanged by ciglitazone treatment while gluconeogenesis from [14C]-alanine was reduced. These findings show that ciglitazone produces its hypoglycemic effect by improving the insulin sensitivity in skeletal muscle, as others have reported in the adipose tissue. The presence of elevated plasma levels of corticosterone and lower levels of insulin in ciglitazone-treated ob/ob mice suggests that the adrenal glucocorticoids are responsible for the basal defects in glucose transport and the hyperinsulinemia is responsible for the insulin insensitivity.

Adrenal Cortex↗
PubMed1986

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue.

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.

Adipose Tissue, Brown↗
PubMed1986

Effect of mazindol, d-amphetamine and diethylpropion on purine nucleotide binding to brown adipose tissue.

Amphetamine, diethylpropion and mazindol were administered to rats in both acute and chronic experiments to measure the changes in purine nucleotide (GDP) binding to the mitochondria from interscapular brown adipose tissue. There was a dose-dependent response to acute treatment with mazindol, but no such effect with diethylpropion. The effects of mazindol and amphetamine were present as early as 3 hours after treatment, and persisted for at least 48 hours, when compared to vehicle-injected rats when all rats were fasted from the time of injection until study. There was no effect when these drugs were added in vitro to mitochondria from brown adipose tissue. Diethylpropion had no effect on GDP binding either in vivo or in vitro at any of the times tested. Following 11 days of treatment with diethylpropion, amphetamine or mazindol, there was a significant increase in purine nucleotide (GDP) binding to mitochondria only in the amphetamine-treated animals. There was no difference in body weight or food intake with any of the three drugs after the third day of chronic treatment. The differences between the effects of these three drugs and those of fenfluramine are discussed in terms of their different central mechanisms of action.

Adipose Tissue, Brown↗
PubMed1986

Role of adrenal glands in the development of abnormal glucose and insulin homeostasis in genetically obese (ob/ob) mice.

This study evaluates the role of adrenal hormones in the development of hyperinsulinaemia and impaired glucose homeostasis in genetically obese hyperglycaemic C57BL/6J ob/ob mice. Lean (+/?) and obese mice were bilaterally adrenalectomised or sham operated at 5 weeks of age, and glucose tolerance was examined after 7 and 14 days. Adrenalectomy temporarily reduced food intake and body weight gain in lean mice, and improved glucose tolerance without a significant change in plasma insulin concentrations at both intervals studied. In obese mice adrenalectomy permanently reduced body weight gain and food intake to values comparable with lean mice. Glucose tolerance was improved in adrenalectomised obese mice at both intervals studied, resulting in plasma glucose concentrations similar to adrenalectomised lean mice. Plasma insulin concentrations during the tolerance tests were reduced in adrenalectomised obese mice, but remained higher than in lean mice. Adrenalectomy did not improve the poor insulin response to parenteral glucose in obese mice. The results indicate that adrenal hormones play an important role in the development of glucose intolerance and contribute to the hyperinsulinaemia in obese (ob/ob) mice, in part by promoting hyperphagia.

Adrenal Glands↗
PubMed1986

Effect of adrenalectomy on the pancreas of db/db mice.

Adrenalectomy has been performed in the diabetic mouse and the islet immunohistochemistry studied. Adrenalectomy restored blood glucose to normal. Mean islet size of diabetic animals was larger than that of either adrenalectomized diabetic animals or of lean controls. Adrenalectomy restored the immunohistochemical appearance of the islets to normal when examined with anti-insulin, anti-glucagon and anti-somatostatin antisera.

Adrenalectomy↗