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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 307 records · Page 17Linked to original sources
PubMed1986

Comparison of ventromedial and paraventricular lesions in rats that become obese.

Lesions in the ventromedial hypothalamus (VMH) uniformly produced obesity, but lesions in the paraventricular nucleus (PVN) produced obesity in only half of the animals. The obesity in the PVN-lesioned animals was related to the extent of PVN damage and was attenuated by concurrent damage to the dorsomedial nucleus. Comparing the PVN-lesioned rats that became obese with the VMH-lesioned rats that showed comparable weight gain, revealed several differences. The nocturnal intake of food in rats eating ad libitum was lower in the VMH-lesioned rats. Glucose concentrations were also lower in the VMH-lesioned rats, whether eating ad libitum or pair fed. Insulin concentrations were higher in the fatter animals fed ad libitum regardless of the location of the lesion. After pair feeding the insulin values were lower in both VMH- and PVN-lesioned rats than in controls. The diurnal excursion of corticosterone was blunted by both hypothalamic lesions in rats fed ad libitum, but after pair feeding there was less distortion of the diurnal rhythm. These data show that the characteristics of obesity produced by PVN lesions differ from those resulting from VMH damage.

Animals↗
PubMed1986

Effect of vagotomy on serum insulin in rats with paraventricular or ventromedial hypothalamic lesions.

The effects of vagotomy on plasma glucose and insulin levels in rats with paraventricular nuclear (PVN) or ventromedial hypothalamic (VMH) lesions were measured during a constant glucose infusion. In one experiment, vagotomy was performed 50 min after the lesions, and in a second experiment, it was performed at the same time as the lesions. After the introduction of lesions in the PVN, there was a significantly greater rise in plasma glucose than in animals with either large or small VMH lesions, both of which had plasma glucose values similar to those in the sham-lesioned animals. The rise in insulin was greater in all three lesion groups than in the sham-operated animals. Although both plasma glucose and insulin had begun to decline before the vagotomy performed 50 min after lesioning, there was a further subsequent fall after vagotomy which was greater in the VMH-lesioned animals with large lesions than in rats with PVN lesions or small VMH lesions. In the sham-lesioned rats, there was no significant change in insulin or glucose after vagotomy. When the vagotomy and hypothalamic lesions were performed simultaneously, the glucose and insulin values in all groups were the same. The present experiments suggest that VMH and PVN exert different controls over pancreatic hormone secretion. The VMH lesions appear to remove an inhibitory effect on the vagus, with resultant hyperinsulinemia in the absence of hyperglycemia. The PVN-lesioned animals show a hyperglycemia which is abolished by vagotomy, suggesting that the PVN connects to vagal fibers which activate the glucagon secretory system in the alpha-cell of the pancreas.

Animals↗
PubMed1986

Autonomic and endocrine factors in the regulation of energy balance.

The regulation of energy reserves is modified by both the autonomic nervous system and the hormonal milieu. The activity of the two limbs of the autonomic nervous system shows a reciprocal response to stimulation or damage in either the ventromedial or the lateral hypothalamus. Ventromedial hypothalamic lesions decrease the activity of the sympathetic nervous system and increase the activity of the vagus nerve. Lateral hypothalamic lesions, on the other hand, increase the activity of the sympathetic nervous system. Central neurotransmitters involved in energy balance include the monoamines, amino acids, and peptides. Removal of adrenal steroids by adrenalectomy reverses or attenuates all forms of obesity by reducing food intake and possibly by increasing energy expenditure. Acute insulin injections increase food intake, but chronic injections may reduce it. A model showing the reciprocal relation of sympathetic activity to energy reserves is presented.

Animals↗
PubMed1985

Dietary obesity: effects of drugs on food intake in S 5B/P1 and Osborne-Mendel rats.

The effect of several drugs on food intake has been examined in two strains of rats, one (S 5B/P1) which is resistant to developing obesity when eating a high fat diet, and one (Osborne-Mendel) which readily develops obesity when eating the same diet. Insulin and 2-deoxy-D-glucose increased food intake in a dose dependent manner in both S 5B/P1 and Osborne-Mendel rats. However, the S 5B/P1 rats showed a greater response, with a shorter latency period, to both agents than did the Osborne-Mendel rats. Conversely, d-amphetamine at the higher doses produced a dose dependent suppression of food intake with maximal suppression being similar for both strains. At a lower dose, however, d-amphetamine significantly increased food intake in the Osborne-Mendel rats, but not in the S 5B/P1 rats. The S 5B/P1 rats were also slightly more sensitive to the anorexic effects of lower dose adenosine than were the Osborne-Mendel rats whereas the reverse was true following higher dose adenosine. Naloxone suppressed food intake equally in both strains and D-glucose did not alter food intake in either strain. These studies identify three drugs, all stimulatory, to which the two strains of rat respond differently.

Adenosine↗
PubMed1985

Effect of fenfluramine on GDP-binding to brown adipose tissue mitochondria.

These experiments have tested the effects of treatment with fenfluramine on the GDP-binding to mitochondria isolated from interscapular brown adipose tissue in vitro. In acute studies, the binding of GDP was significantly increased after 3, 24, and 48 hours of treatment with a single dose of 20 mg/kg of body weight. Addition of fenfluramine in vitro, however was without effect. In a dose-response study there was no significant increase with doses of 2 or 6 mg/kg but there was a significant increase at 20 mg/kg. During eleven days of treatment, food intake was initially depressed by fenfluramine (20 mg/kg) and body weight was significantly reduced. By the ninth day of treatment however, food intake had returned to control values but the body weight remained significantly lower than in the control group. The weight of interscapular brown adipose tissue was not significantly altered but binding of GDP to isolated mitochondria was increased by 55%. These studies suggest a thermogenic effect of fenfluramine on the brown adipose tissue of rats.

Adipose Tissue, Brown↗
PubMed1985

Autonomic and endocrine factors in the regulation of food intake.

Destruction of the ventromedial hypothalamus produces hyperphagia, hyperinsulinemia and hypertriglyceridemia. These changes appear to be partly the result of increased firing rate of the vagus nerve and reduced firing rate of the sympathetic nerves. These reciprocal changes in the function of the autonomic nervous system appear to provide an adequate explanation for the hyperinsulinemia in this syndrome, and for the reduced heat expenditure. Destruction of the lateral hypothalamus, has effects opposite to those of the ventromedial hypothalamus with a reduction in food intake, a decrease in body fat, and an increase in the activity of the sympathetic nervous system. These reciprocal functions of the hypothalamus are associated with different adrenergic receptors. A medial hypothalamic alpha-adrenergic system mediates the epinephrine stimulation of feeding, and a beta-adrenergic system mediates the lateral hypothalamic inhibition of eating. Peptides from the endorphin family can stimulate food intake, but most other peptides are inhibitory. Growth hormone and thyroid hormone stimulate food intake under appropriate conditions. Insulin and adrenal steroids appear to play the most important role of all the hormones in regulating food intake. Deficiency of adrenal glucocorticoids is associated with decreased food intake and a wasting of body flesh. Increased levels of glucocorticoids, on the other hand, produce a variety of truncal obesity. In animals with ventromedial hypothalamic lesions and obesity, adrenalectomy will reverse the obesity. In genetically obese rats and mice, adrenalectomy will attenuate the progression of the syndrome. These effects appear to be through a reduction of food intake, and an increase in energy expenditure. Injections of insulin will stimulate food intake and may lead to obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1985

Meal-induced brown fat thermogenesis and thyroid hormone metabolism in rats.

The relationship between the meal-induced increase in brown adipose tissue (BAT) thermogenesis, determined by the level of GDP binding to BAT mitochondria, and thyroid hormone metabolism have been examined. A single low-protein, high-carbohydrate meal resulted in a significant increase in the thermogenic activity of BAT. This effect on BAT thermogenesis was accompanied by significant increases in activity of thyroxine 5'-monodeiodinase in the BAT (P less than 0.05) and liver (P less than 0.02) but not with any significant changes in serum concentrations of the thyroid hormones. The stimulatory effects of the meal on BAT thermogenesis and hepatic thyroxine (T4) to triiodothyronine (T3) conversion persisted at least as late as 24 h after meal onset. Food deprivation for 40 h was associated with large reductions in serum concentrations of T3 (P less than 0.01) and T4 (P less than 0.001), but deprivation for 18 h had no significant effect on serum T3 and T4 concentrations. Our data indicate that the meal-induced increase in BAT thermogenesis can be independent from changes in serum concentrations of thyroid hormones and suggest that T3 produced in BAT in response to feeding may play a role in the thermic response of this tissue to meals.

Adipose Tissue, Brown↗
PubMed1985

Guanosine diphosphate binding to brown adipose tissue mitochondria is increased after single meal.

A single meal results in an increased thermic activity of brown adipose tissue (BAT). The purpose of the present studies was threefold: 1) to identify major metabolic origins involved in this thermic response, 2) to determine the effect of meal composition on it, and 3) to determine time changes in postprandial brown fat thermogenesis. Wistar rats were trained to eat during 2 feeding sessions/day. On the days of the experiment, rats received a test meal for 2 h, and respective control rats were simultaneously meal deprived. The animals were killed at one or more time points after meal onset, and their BAT was removed for determination of mitochondrial guanosine diphosphate (GDP) binding to indicate rate of uncoupled respiration (expts 1 and 3) or Na+-K+-ATPase activity representing coupled respiration (expt 2). Meal taking was followed by an 85% increase in GDP binding (P less than 0.001). In contrast, Na+-K+-ATPase activity was not altered by a test meal of a similar composition. The largest meal-induced rise in mitochondrial GDP binding was evident during the early postprandial hours, and it was greatly reduced by 10 h after meal onset. Expressed per total interscapular brown fat depot, a high-carbohydrate meal caused a greater increase in GDP binding than an equicaloric high-fat meal. Our data indicate that the BAT proton conductance pathway is activated by a single meal.

Adipose Tissue, Brown↗
PubMed1985

Interaction of light and corticosterone on food intake and brown adipose tissue of the rat.

The food intake of sham-operated and adrenalectomized rats was measured in 12-h intervals with animals housed in either alternating periods of 12:12 light-dark or in continuous light. The food intake with alternating light and dark was unaffected by adrenalectomy. The maintenance of a constant infusion of corticosterone in adrenalectomized rats also did not disturb the pattern of food intake. In continuous light, food intake was not significantly different in each 12-h period of the daily cycle. Neither adrenalectomy nor the injection of corticosterone, 240 micrograms/day, altered the average 12-h food intake in rats in constant light. The weight of interscapular brown adipose was smaller in adrenalectomized animals, but the protein content was unaffected. Adrenalectomy significantly increased the specific binding of the purine nucleotide GDP to mitochondria from brown adipose tissue. This specific binding was restored to normal by either corticosterone infusion or injection. We conclude that light is the principal entrainer for the average food intake during 12-h periods and that within the framework of these experiments corticosterone plays an insignificant role in controlling food intake. However, adrenalectomy did significantly increase the purine nucleotide binding to mitochondria from brown adipose tissue.

Adipose Tissue, Brown↗
PubMed1985

Complications of obesity.

The major diseases associated with obesity are hypertension, atherosclerosis, and diabetes, as well as certain types of cancer. Less well-known complications include hepatic steatosis, gallbladder disease, pulmonary function impairment, endocrine abnormalities, obstetric complications, trauma to the weight-bearing joints, gout, cutaneous disease, proteinuria, increased hemoglobin concentration, and possibly immunologic impairment. A U- or J-shaped curve illustrates the relation between body mass index and the degree of these various complications. This relationship can be used to provide guidelines for assessing treatment of obesity.

Adult↗
PubMed1984

Adrenalectomy increases norepinephrine turnover in brown adipose tissue of obese (ob/ob) mice.

The hyperphagia and rapid body weight gain normally observed in young obese (ob/ob) mice were abolished by removal of their adrenal glands, whereas food intake and weight gain of lean mice were not significantly affected by adrenalectomy. Adrenalectomy lowered body energy density (kcal/g carcass) in obese mice more than could be attributed to reduced food intake per se, suggesting that their energy expenditure was also increased. In control obese mice, low stimulation of brown adipose tissue by the sympathetic nervous system, as indicated by the low fractional rates of norepinephrine (NE) turnover in their brown adipose tissue may have contributed to the reduced energy expenditure in these animals. Adrenalectomy increased the rates of NE turnover in brown adipose tissue of obese mice to rates nearly equal to those observed in lean mice without affecting NE turnover in this tissue of lean mice. Likewise, removal of the adrenals normalized the low rates of NE turnover in hearts of obese mice without affecting lean mice. Rates of NE turnover in two other organs, white adipose tissue and pancreas, of control and adrenalectomized obese mice were similar to rates observed in lean counterparts. The adrenal may thus contribute to both the hyperphagia and the low energy expenditure by brown adipose tissue that together cause gross obesity in ob/ob mice.

Adipose Tissue, Brown↗
PubMed1984

Effects of oral and parenteral quinine on rats with ventromedial hypothalamic knife-cut obesity.

The addition of quinine to the food reversed the obesity in rats with hypothalamic hyperphagia induced by knife cuts. Similarly, the injection of quinine into rats with hypothalamic knife cuts reduced food intake and body weight but the effects were smaller than those observed when quinine was added to the diet. Urinary quinine excretion was similar by the oral and parenteral routes. The food intake of the knife-cut animals receiving quinine gradually fell to the same level as in the sham-operated animals receiving quinine by either route. The weights of retroperitoneal fat pads were related to the weights of the animals and were reduced in the quinine-treated groups. Plasma insulin concentrations were significantly higher in the knife-cut animals and were reduced toward control levels by quinine treatment. Gluconeogenesis, measured by incorporation of radioactivity from labeled bicarbonate into glucose, was unaffected by treatment with quinine or by knife cuts. Lipogenesis from tritiated water in vivo was not different between treatment groups in the liver or retroperitoneal fat pads. However, in vivo lipogenesis was reduced in knife-cut rats fed ad libitum compared with quinine-treated rats. The response of lipogenesis to insulin in vitro was also not different between treatment groups. These data suggest that a major part of the reduction in food intake in hyperphagic rats eating a quinine-adulterated diet is due to postingestional events.

Adipose Tissue↗
PubMed1984

Effect of prandial glucose on brown fat thermogenesis in rats: possible implications for dietary obesity.

We have previously shown that a single meal results in an increased thermic activity of brown adipose tissue (BAT). In the present study, we examine the importance of the availability of glucose in the test meal and in the incubation medium on the rate of in vitro respiration of BAT. We show that a high glucose test meal results in a significant increase in BAT weight and in its in vitro rate of respiration and that the effect of the high glucose meal on brown fat thermogenesis is significantly greater than that of an equicaloric high fructose meal. These data suggest that a decreased postprandial BAT thermogenesis may contribute to the increased metabolic efficiency and to the obesity reported to be associated with sucrose consumption in the rat. We also show that the reduced in vitro rate of respiration of consumption in the rat. We also show that the reduced in vitro rate of respiration of BAT from meal-deprived rats is largely corrected by the addition of glucose and insulin to the incubation medium.

Adipose Tissue, Brown↗
PubMed1984

Adrenalectomy reverses insulin resistance in muscle from obese (ob/ob) mice.

Glucose transport and insulin resistance in the skeletal muscle of the genetically obese (ob/ob) mouse has been studied in animals at 6-7 wk of age using an in situ perfused hindquarter preparation. Rates of glucose uptake and the uptake of radioactively labeled 2-deoxy-D-glucose were lower in muscles from intact ob/ob mice than in those from their lean littermates. Following adrenalectomy the basal rate of glucose or 2-deoxy-D-glucose uptake in the ob/ob mice was restored to normal. The uptake of 2-deoxyglucose was tested at two insulin concentrations. In lean mice, adrenalectomy had no effect on 2-deoxyglucose uptake. Adrenalectomy, however, restored the responsiveness to insulin in the ob/ob mouse to normal. The activity ratio of muscle glycogen synthase was elevated by insulin but the effect was greater in the lean animals with or without adrenal glands than in the obese mouse. Adrenalectomy in the obese mouse did not correct this defect.

Adrenal Glands↗