Search PubMed⌕ Search

Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 325 records · Page 18Linked to original sources
PubMed1984

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

After adrenalectomy in obese mice the rate of weight gain parallels that in lean controls and falls progressively behind that in intact ob/ob mice. Food intake was reduced to normal, but the body temperature of adrenalectomized ob/ob mice was similar to that of intact ob/ob mice and remained below that of control lean mice. After exposure to an ambient temperature of 6 degrees C the body temperature in adrenalectomized ob/ob mice fell at the same rate as in intact ob/ob mice. The increase in tail length, brain weight, spleen weight, and muscle weight after adrenalectomy in ob/ob mice could not be duplicated by reducing the weight gain of ob/ob mice to that of the adrenalectomized mice. Similarly the induction of obesity with gold thioglucose significantly increased the weight of the gastrocnemius muscle and spleen rather than lowering it to levels found in ob/ob mice. Treatment of adrenalectomized ob/ob mice with cortisone acetate, but not with deoxycorticosterone acetate (DOCA), reduced muscle weight, spleen weight, brain weight, and the growth in tail length. Both cortisone and DOCA increased food intake, liver weight, growth rate, and the weight of the adipose tissue in ob/ob mice. These effects are significantly greater than observed in comparably treated lean animals and suggest that glucocorticoids of adrenal origin play an integral role in the phenotypic expression of genetic obesity. These data also indicate that the hypothermia is not a sufficient cause of the obesity in the ob/ob mice, since hypothermia persists in the adrenalectomized mice, but when food intake falls to normal there is no progression of the obesity.

Adrenalectomy↗
PubMed1984

Catecholamine turnover in rats with ventromedial hypothalamic lesions.

The disappearance of norepinephrine (NE) from brown adipose tissue, heart, and pancreas in vivo has been examined in rats with ventromedial hypothalamic (VMH) lesions and in appropriate control rats. Two weeks after the introduction of these lesions, the rate of NE turnover following blockade of NE synthesis with alpha-methyl-p-tyrosine was significantly greater in brown adipose tissue and heart of rats with VMH lesions than in sham-operated controls. This significant increase occurred whether the animals were fed ad libitum or pair-gained to the sham-operated controls. In the pancreas, on the other hand, no effects of hypothalamic lesions could be detected. When rats were fasted, NE turnover slowed in both sham-operated and VMH-lesioned rats, but the turnover slowed more in sham-operated than in VMH-lesioned rats. When exposed to the cold for 6 h during measurements of NE turnover, VMH-lesioned rats increased their rate of NE turnover as did sham-operated rats. Fasted animals exposed to the cold had significantly higher rates of NE turnover whether or not they also had VMH lesions. Animals with electrolytic or knife-cut VMH lesions showed comparable rates of NE turnover in the fasted state. Eight weeks after hypothalamic lesions, similar studies were conducted. By this time NE turnover was not significantly different between the VMH-lesioned and sham-operated rats fed ad libitum. However, fasting, which slowed NE turnover in sham-operated rats, had no effect in VMH-lesioned animals. These data are discussed in relation to the autonomic hypothesis.

Adipose Tissue, Brown↗
PubMed1984

Ventromedial hypothalamic knife-cut lesions in rats resistant to dietary obesity.

The effects of ventromedial hypothalamic (VMH) knife-cut lesions on food intake and body weight of S 5B/Pl rats, which are normally resistant to obesity when eating a high-fat diet, were examined in two experiments. In the first experiment body weight increased only slightly after VMH knife-cut lesions when animals were fed pelleted laboratory chow or a 10% corn oil diet. When eating the 30% corn oil diet, however, body weight increased in the VMH knife-cut rats. In the second experiment VMH knife-cut lesions produced a small weight gain in rats fed the 10% fat diet; this manipulation also increased food intake and disrupted the normal diurnal feeding pattern. Changes in the weight of the liver, interscapular brown adipose tissue, and white adipose tissue paralleled the changes in body weight. Plasma insulin increased in the rats eating the 30% corn oil diet ad libitum but not in the VMH-lesioned animals pair fed to the sham-operated rats. Incorporation of 3H from 3H2O into lipid was significantly increased in white fat of animals with VMH knife cuts. Similar results were obtained from incubation of adipose tissue in vitro with insulin and radioactively labeled glucose. These studies show that hypothalamic knife-cut lesions can remove the resistance of the S 5B/Pl rats to obesity when they are fed a high-fat diet.

Adipose Tissue↗
PubMed1984

Catecholamine turnover in S 5B/P1 and Osborne-Mendel rats: response to a high-fat diet.

Catecholamine turnover in response to fasting, cold exposure, and a high-fat diet has been measured in the Osborne-Mendel rat, which readily develops obesity when fed a high-fat diet, and the S 5B/P1 rat, which does not. We have tested the hypothesis that this difference in response to diet might be associated with altered rates of norepinephrine or epinephrine turnover. The endogenous norepinephrine concentration in interscapular brown adipose tissue was significantly greater in fasted S 5B/P1 rats than in fasted Osborne-Mendel rats. The fractional norepinephrine turnover rate in interscapular brown adipose tissue of fasted animals was also greater in the S 5B/P1 rat than in the Osborne-Mendel rat. Cold exposure increased the fractional norepinephrine turnover rate in interscapular brown adipose tissue for both strains of rats but increased the fractional norepinephrine turnover rate in the pancreas in only the Osborne-Mendel rats. The turnover of epinephrine and the adrenal concentration of this hormone were not different between the two strains. Normal and high-fat diets were fed to both strains; the Osborne-Mendel rats were pair fed the high-fat diet to prevent excess weight gain. Endogenous concentrations of norepinephrine in interscapular brown adipose tissue was increased by the high-fat diet; the increase was greater in S 5B/P1 rats. The high-fat diet resulted in increased norepinephrine turnover in interscapular brown adipose tissue of the S 5B/P1 rat but not the Osborne-Mendel rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1984

Muscle protein turnover in the perfused hindquarters of lean and genetically obese-diabetic (db/db) mice.

The stability of the perfused mouse hindquarter was assessed for a period of 5 h, and the preparation shown to remain stable for metabolic studies over this time period. Muscle protein synthesis and degradation rates in lean and diabetic-obese (db/db) mice were measured using the in situ perfused hindquarter preparation. The rates of protein synthesis were 48% lower in the muscles of intact db/db mice than in the lean controls when expressed per gram TCA precipitable protein and 46% lower when expressed per gram dry weight. Adrenalectomy, which has been shown to restore the lean body mass of the db/db mice to normal, had the effect of returning protein synthesis rate in muscle of db/db mice to lean control values. Insulin at a dose of 1 mU/ml stimulated protein synthesis in lean mice only, showing that the process of protein synthesis in the db/db mice is also insensitive to insulin. Measurements of the rates of degradation of muscle protein showed no differences between lean and db/db mice. These findings suggest that the decreased lean body mass of db/db mice is the result of a defect in protein synthesis rather than due to altered degradation.

Adrenalectomy↗
PubMed1984

Hypothalamic and genetic obesity: an appraisal of the autonomic hypothesis and the endocrine hypothesis.

Several lines of evidence support the hypothesis that derangements in the function of the autonomic nervous system play an important role in the development of hypothalamic obesity. Vagotomy below the diaphragm reverses the syndrome. In diabetic rats cured of their diabetes with transplants of fetal pancreatic tissue beneath the renal capsule, ventromedial hypothalamic (VMH) lesions do not produce the characteristic rise in food intake nor do they significantly increase serum insulin. These observations indicate that the hyperinsulinaemia following VMH lesions is the result of neural connections rather than from a circulating humoral factor released following VMH injury. The smaller salivary glands, reduced level of glucagon and impaired mobilization of fatty acids during stress in VMH lesioned rats point to reduced activity of the sympathetic nervous system. The impaired mobilization of fat from retroperitoneal depots in VMH lesioned rats during fasting is similar to the effect of sympathetic denervation of the retroperitoneal fat pad. The turnover of norepinephrine in tissues innervated by the sympathetic nervous system is either reduced or less responsive to nutritional influences after VMH lesions. The thermogenic activity of brown adipose tissue is also impaired after VMH lesions, presumably as a result of reduced sympathetic firing rate of nerves innervating the BAT. In contrast to the reduced activity of the sympathetic nervous system after Vmh lesions there is increased activity after electrolytic lesions of the lateral hypothalamus. Collectively these data indicate that the autonomic nervous system plays a central role in the regulation of metabolic functions following disturbances of hypothalamic function. The concept of the thrifty gene as a mechanism for the development of obesity has been explored in several models. The efficiency with which food is stored as fat appears to be increased in all forms of experimental obesity. Studies in the genetically obese mouse have documented this phenomenon most elegantly. In one experiment animals carrying a double dose of the gene for obesity received exactly the same quality of food on exactly the same schedule throughout a 24 hour period of time as their lean littermates yet gained more body weight and more fat. In a second experiment the importance of a thrifty gene was documented by comparing the rates of weight loss and survival time in homozygous and heterozygous lean animals. Heterozygosity improved survival compared to the homozygous lean animal indicating the value of the genetic trait for survival in the wild.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue, Brown↗
PubMed1984

Cholecystokinin, bombesin and neurotensin in brain tissue from obese animals.

The concentration of cholecystokinin (the octapeptide, CCK-8), bombesin, and neurotensin was measured by radioimmunoassay in the cortex, hypothalamus and diencephalon of brains from lean, genetically obese and hypothalamic (VMH) obese rodents. Highest concentration of CCK-8 was found in the cortex whereas highest concentrations of bombesin and neurotensin were in the hypothalamus. When food was provided ad libitum, there was no difference in concentration of any of these peptides between lean and the respective genetically obese mice (ob/ob) and fatty (fa/fa) rats, or between lean and hypothalamic (VMH lesioned) obese rats. Adrenalectomy, which arrested the progression of obesity in both ob/ob and fatty rats, did not result in significant change in concentration of any of the three peptides studied in comparison with the respective sham-operated animals. Though significant differences in cholecystokinin and bombesin concentrations were detectable in some instances between adrenalectomized lean and adrenalectomized obese rats, these differences did not appear to be related to fall in food intake or slowing of body weight gain. Thus a variety of manipulations which altered the nutritional plane of the experimental rodents was not accompanied by significant changes in brain concentrations of cholecystokinin, bombesin or neurotensin.

Adrenal Glands↗
PubMed1983

Compositional and metabolic changes in brown adipose tissue following a single test meal.

In rats maintained on a scheduled feeding plan, the hypertrophy of brown adipose tissue (BAT) observed after a low-protein/high-carbohydrate single test meal was accompanied by significant changes in the percentage of all major constituents of the tissue. There was a fall in the percentage of water (P less than 0.01), a rise in the percentage of fat (P less than 0.05), and a rise in the percentage of glycogen (P less than 0.001). The largest absolute changes following a meal were in the fat content, which almost doubled, and in the glycogen content, which exhibited about a four-fold increase. Deposition of fat in the BAT following the test meal was accompanied by a three-fold increase in the rate of fatty acid synthesis (P less than 0.05). The in vitro respiration rate of BAT was usually significantly increased in the meal-fed rats, but the effect of replacing the protein content of the test meal with starch was not clear. A lower protein, higher starch diet (9% of calories from protein, 72% from starch) resulted in a trend for a larger thermic effect than a higher protein, lower starch diet (27% of calories from protein, 54% from starch).

Adipose Tissue, Brown↗
PubMed1983

Ovarian hormones influence brown adipose tissue.

Adult female rats were ovariectomized (OVX) or sham-operated and 4-5 weeks later OVX groups were treated with estradiol benzoate (EB), progesterone, both hormones, or the oil vehicle. All rats were sacrificed on the 4th day of hormone treatment following an overnight fast and a terminal meal. Interscapular brown adipose tissue (BAT) pads of EB-treated groups were heavier and contained more lipid than those of the other OVX groups. Lipid content of adipose tissue differed according to site (BAT less than inguinal less than parametrial = retroperitoneal), but only BAT exhibited differential responsiveness to hormonal treatments. There was also a trend for increased oxygen consumption by BAT from EB-treated rats. It is concluded that BAT may be involved in the process of increased energy expenditure by estrogen-treated rats.

Adipose Tissue, Brown↗
PubMed1983

Hyperinsulinemia in rats with hypothalamic obesity: effects of autonomic drugs and glucose.

The present study examined the effects of autonomic drugs and glucose on the insulin and glucose concentrations of sham-operated rats and of rats with ventromedial hypothalamic (VMH) lesions and obesity. In the basal condition both epinephrine and atropine significantly decreased serum insulin levels in VMH-lesioned but not sham-operated rats. During glucose stimulation of insulin secretion in VMH-lesioned rats, epinephrine inhibited the increase of insulin by 83% and atropine inhibited it by 42%; whereas in sham-operated rats, epinephrine inhibited it by 70% and atropine inhibited it by 34%. Epinephrine with atropine completely blocked the increase of insulin in response to glucose in both VMH-lesioned and sham-operated rats. In the basal condition, epinephrine together with propranolol significantly decreased serum insulin levels in VMH-lesioned but not sham-operated rats. Epinephrine with phentolamine, on the other hand, markedly increased insulin in the VMH-lesioned rats and to a lesser degree in the sham-operated rats. During glucose stimulation epinephrine with propranolol inhibited the increase of insulin in both groups. Epinephrine with phentolamine or isoproterenol markedly increased serum insulin in VMH-lesioned rats. These results suggest that stimulation of the vagus nerve and increased sensitivity of the beta-receptors on the beta-cells of the islet contribute to the development of hyperinsulinemia. The sympathetic contribution may also be through suppression of alpha-adrenergic receptors.

Animals↗
PubMed1983

Lateral hypothalamic lesions and norepinephrine turnover in rats.

Animals with lateral hypothalamic lesions lost significantly more weight in the 18 h following this lesion than did sham-operated animals or rats with cerebral cortical lesions deprived of food for the same time period. In the acutely fasted sham-operated animals the turnover of norepinephrine in interscapular brown adipose tissue, heart, and pancreas was slowed but in fasted rats with lateral hypothalamic lesions norepinephrine turnover rates were three- to ninefold faster in all three organs. Exposure to the cold (4 degrees C) significantly increased norepinephrine turnover in the interscapular brown adipose tissue, heart, and pancreas of fasted sham-operated rats, but did not further increase the rate of turnover in lateral hypothalamic-lesioned rats. Rats with lesions in the cerebral cortex responded in a fashion similar to that of the sham-operated animals. Gastric erosions and microhemorrhagic gastric mucosa were observed in five of six acutely fasted rats with lateral hypothalamic lesions whereas all sham-operated rats had a normal appearance of the stomach lining. Animals with lateral hypothalamic lesions made 3 wk earlier also showed an increased rate of norepinephrine turnover in the interscapular brown adipose tissue, heart, and pancreas following an 18 h fast. Rats with bilateral lesions in the paraventricular region of the hypothalamus, however, responded similarly to sham-operated animals with a reduction in the turnover in norepinephrine with fasting and an increase in norepinephrine turnover rate after cold exposure even with fasting. These data suggest that lateral hypothalamic lesions produce an acute increase in turnover of norepinephrine, and that this increased turnover persists for up to 3 wk.

Adipose Tissue, Brown↗
PubMed1983

Diurnal rhythm for corticosterone in obese (ob/ob) diabetes (db/db) and gold-thioglucose-induced obesity in mice.

The present studies have examined the diurnal rhythm of corticosterone in genetically obese mice and in mice made obese by treatment with gold thioglucose. The values of corticosterone were significantly higher in the ob/ob mice than in lean mice at each of the four time points measured. The diurnal pattern for corticosterone in ob/ob mice, however, was similar to that in lean mice at both 6 and 12 weeks of age and had a nadir at 0700 h and a zenith at 1800 h. In mice with gold thioglucose-induced obesity, on the other hand, the corticosterone values were the same in the obese and lean control mice 6 weeks after treatment with gold thioglucose. By 12 weeks after gold thioglucose treatment, the obese animals had higher corticosterone levels in the morning than lean animals, but the peak values at 1800 h were not different. Restriction of body weight gain by allowing obese and lean mice food for only 4 h daily altered the pattern of corticosterone, but the values in the ob/ob mice remained higher than those in the lean mice. The corticosterone values of db/db mice housed at 24 C were significantly higher at 0800 and 1800 h than those in lean mice, and the diurnal rhythm was present, but smaller, in the db/db mice. In db/db and lean mice housed at an ambient temperature of 33 C, the corticosterone concentrations increased to the same values, and the diurnal rhythm was blunted in both. At the higher ambient temperature, the db/db mice gained weight more slowly, whereas the lean mice showed no weight gain.

Aging↗
PubMed1983

The Prader-Willi syndrome: a study of 40 patients and a review of the literature.

Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature.

Body Height↗
PubMed1982

Sodium potassium dependent ATPase in hypophysectomized rats: response to growth hormone, triiodothyronine, and cortisone.

Groups of hypophysectomized rats were treated with pharmacologic doses of growth hormone, triiodothyronine or cortisone acetate alone or with a combination of growth hormone plus triiodothyronine or growth hormone plus cortisone. After a 7 day period of treatment the hydrolysis of ATP in the presence of ouabain (mg ATPase) and in the absence of ouabain (total ATPase) was determined. Ouabain-suppressible sodium, potassium-dependent ATPase or (Na+ + K+) ATPase was calculated as the difference in the rate of hydrolysis in the presence and absence of ouabain. The activity of the Mg ATPase was significantly reduced in brain after treatment with growth hormone regardless of whether other hormone. In liver there was a significant increase in (Na+ + K+) ATPase in growth hormone, triiodothyronine, or (Na+ + K+) ATPase but there was no effect of triiodothyronine or cortisone and no interaction with the effect of growth hormone. In liver there was a significant increase in (Na+ + K+) ATPase in growth hormone, triiodothyronine, or cortisone-treated animals but Mg ATPase was unaffected by hormone treatment except for the group receiving both growth hormone and cortisone. In kidney homogenates both growth hormone and triiodothyronine significantly increased the activity of the (Na+ + K+) ATPase. There was no effect of cortisone. These data suggest that growth hormone and triiodothyronine may both be calorigenic through their effect on the sodium pumping mechanism in the call membrane.

Animals↗