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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 19 recordsLinked to original sources
PubMed1992

Effects of cholecystokinin on sympathetic activity to interscapular brown adipose tissue.

The effects of injecting cholecystokinin (CCK) into the third ventricle or into selected hypothalamic sites on electrical firing rate of sympathetic nerves to interscapular brown fat (IBAT) has been investigated in anesthetized rats. The hypothesis for these experiments was that there was a reciprocal relationship between sympathetic activity and food intake. Since CCK reduces food intake we predicted that CCK would stimulate sympathetic activity to IBAT. Following the injection of CCK into the third ventricle there was an increase in firing rate of sympathetic nerves to IBAT. When the peptide was injected into either the ventromedial hypothalamic nucleus (VMH) or lateral hypothalamic area (LHA), there was likewise an increase in sympathetic firing rate. The injection of CCK into the paraventricular nucleus produced a small decrease in sympathetic firing rate. In contrast, no effect was seen following injection of CCK into the preoptic area or dorsomedial hypothalamic nucleus. Thus, the VMH or LHA appear to be the principal hypothalamic areas mediating the stimulation of sympathetic activity to IBAT which is observed following the third ventricular injection of CCK. These studies support the hypothesis of a reciprocal relationship between the effects of CCK on the thermogenic component of the sympathetic nervous system and food intake and identify the VMH and LHA as the primary sites for this effect.

Adipose Tissue, Brown↗
PubMed1992

Food intake of lean and obese Zucker rats following ventricular infusions of adrenergic agonists.

The effect on food intake of adrenergic agonists administered into the third cerebral ventricle was studied in Zucker fatty and lean rats. The alpha 2 agonist, clonidine, produced a larger dose-related increase in food intake in lean rats than in the fatty rats. Dose-response curves show similar sensitivity, but decreased responsiveness in the lean animal. The beta 2 adrenergic agonist, salbutamol, produced similar food effect in obese and lean rats reducing food intake in the lean rats at the highest dose (300 nmol), and in the fatty rats at the two highest doses. The effects were small in both groups. The beta 3 agonist, BRL 37344, ([4-(2-((2-hydroxy-2-(3-chlorophenyl)ethyl)amino)-propyl)-phenoxy acetate]) produced a larger dose-related decrease in food intake in the fatty rat than in the lean rats. Dose-response curves showed that sensitivity of beta-receptors was similar, but the lean animals were less responsive. The beta-adrenergic blocking drug propranolol blocked the anorectic effect of BRL 37344 in the fatty rat. These studies suggest that in the fatty rat, the alpha 2 receptor system is tonically more active and the beta 3 receptor system tonically less active, a relationship that would explain the hyperphagia and development of obesity in these animals.

Adrenergic beta-Agonists↗
PubMed1992

Genetic, hypothalamic and endocrine features of clinical and experimental obesity.

Obesity occurs in both clinical and animal forms in a variety of specific models which allow study of its underlining endocrine and mechanistic features. Among the neuroendocrine varieties of obesity, polycystic ovaries are probably the most common. The importance of the gonadal feedback system for regulation of food intake and obesity is indicated by the effects of castration in experimental animals which is a widely used mechanism for producing experimental obesity. Cushing syndrome and hypothalamic obesity are rare clinical syndromes. The current evidence suggests that there are two types of hypothalamic obesity from a mechanistic point of view--one associated with hyperphagia as a necessary and sufficient cause and a disturbance of the autonomic nervous system without hyperphagia as a second mechanism. Although genetic factors underlie most types of human obesity, there are several dymorphic forms of obesity including the Prader-Willy syndrome, Cohen's syndrome, Carpenter's syndrome, Ahlstrom's syndrome and the Bardet-Biedel syndrome. The Prader-Willi syndrome is characterized by obesity hypotonia hypogonadism and mental retardation. In animals, a dominant form of inheritance of obesity is seen in the yellow mouse. Current evidence suggests that this syndrome can be explained by reduced acetylation of MSH in the pituitary and/or hypothalamus. Several recessively inherited forms of obesity exist including the obese mouse, the diabetes mouse, fatty rat, the fat mouse, tubby mouse and the corpulent rat. In addition, there are a number of polygenic types of experimental obesity. The final mechanistic classification of obesity are those due to dietary manipulation. For both human beings and animals, a highly fat diet appears to be particularly problematic for the development of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A survey of the opinions of obesity experts on the causes and treatment of obesity.

A survey of opinions on the causes and effectiveness of treatment of obesity was carried out on 50 physicians and scientists involved in obesity research. Responses were grouped by region (Europe, North America, and United Kingdom), sex, age (30-50 and greater than 50 y) and degree (MD or PhD). Genetic factors were considered the most important causes of obesity overall. Females viewed lack of physical activity, carbohydrate craving, and weight cycling as significantly more important causes than did their male colleagues and viewed exercise as a more effective treatment. There were regional variations in the assessment of the importance of metabolic defects and weight cycling as causes of obesity and in the usefulness of diet in the treatment of obesity. The older group of respondents rated low-fat diet more highly as a treatment than did their younger colleagues. All groups viewed serotonergic and thermogenic drugs as effective treatments whose usefulness would increase during the next 10 years.

Adult↗
PubMed1992

Peptides affect the intake of specific nutrients and the sympathetic nervous system.

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-melanocyte stimulating hormone increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin-releasing hormone, neurotensin, bombesin, cyclo-his-pro, and thyrotropin-releasing hormone reduce food intake. Many of these peptides have reciprocal effects on food intake and sympathetic activity with those peptides that stimulate food intake reducing sympathetic activity and vice versa. In addition, neuropeptide Y specifically increases carbohydrate intake. Galanin and opioid peptides on the other hand increase fat intake whereas enterostatin reduces fat intake. Glucagon decreases protein intake. The effect of peptides on 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↗
PubMed1992

Pathophysiology of obesity.

Individuals weighing greater than 100 kg represent a small fraction of the population and yet pose a major health risk to themselves. It is proposed that individuals be classified according to their body mass index (BMI). Class 0 individuals have a BMI of 20-25 kg/m2 and are not obese; Class I individuals have a BMI of 25-30 kg/m2 and are at low risk from their obesity; Class II individuals have a BMI of 30-35 kg/m2 and have moderate risk; Class III individuals have a BMI of 35-40 kg/m2 and have high risk associated with their obesity; Class IV individuals have a BMI of greater than 40 kg/m2 and are at very high risk for illness. Class IV is the primary group for surgical consideration. The pathophysiologic consequences of excess weight result in large part from increased food intake and/or decreased physical activity. Individuals in Class IV have additional problems related to their weight, including cardiomyopathy, Pickwickian/sleep apnea syndrome, pituitary/gonadal dysfunction, acanthosis nigricans, and significant osteoarthritis.

Humans↗
PubMed1992

Drug treatment of obesity.

The currently available drugs for treatment of obesity act on two pharmacologic systems in the central nervous system: the noradrenergic system and the serotonergic system. There are clear and convincing clinical data that these drugs are effective and safe. However, several types of barriers exist to their proper and effective use, including public perceptions that obesity is a disease resulting from lack of willpower, professional expectations that anorexiant drugs should cure obesity, hindrance by state licensing agencies, regulatory rigidity, limited research funding, and legislative inaction. In spite of these limitations, several new and potentially valuable drugs are under development, and given an appropriate clinical and therapeutic environment, the future is bright for treatment of obesity.

Humans↗
PubMed1992

Effect of adrenalectomy and high-fat diet on the fatty Zucker rat.

Lean and obese Zucker fatty rats were adrenalectomized or sham operated at 10 wk of age. At 15 wk one-half of each group was placed on a high-fat diet. At 32 wk of age the experiment was ended. Several conclusions can be drawn about the effects of adrenalectomy, high-fat diets, and their interaction in the Zucker fatty rat. First, adrenalectomy slowed the weight gain in both obese fatty rats and in the lean animals, although the effect was greater in the fatty rats. Second, weight gain was accelerated in intact lean and fatty rats eating a high-fat diet. Third, adrenalectomy attenuated the weight gain associated with a high-fat diet and reduced the body content of fat and protein in the lean animals and fatty rats fed the low-fat diet. Fifth, adrenalectomy significantly affected the retroperitoneal and subcutaneous fat depots but not the epididymal fat depot. Sixth, adrenalectomy decreased fat cell number in retroperitoneal and subcutaneous fat depots, but this was much less evident in the epididymal fat depot. Seventh, lipoprotein lipase activity expressed per milligram protein increased after adrenalectomy in the fatty rat but was reduced on the same basis in lean animals regardless of diet. Finally, the increase in retroperitoneal lipoprotein lipase activity expressed per fat cell observed in lean animals fed the high-fat diet was not observed in the fatty rat. These studies show that a high-fat diet and adrenalectomy interact in the development of obesity in both lean and fatty Zucker rats.

Adipose Tissue↗
PubMed1992

Cholecystokinin and satiety: effect of hypothalamic obesity and gastric bubble insertion.

Cholecystokinin (CCK) is a gut peptide whose proposed effect on satiety is thought to be related to gastric volume and to be signaled through vagal afferent fibers to the medial hypothalamus. To test these hypotheses we infused CCK C-terminal octapeptide (CCK-8) or saline in a random double-blind fashion in three groups of subjects: 17 obese subjects, 6 of whom subsequently received a gastric bubble, and 5 obese subjects whose obesity was due to hypothalamic injury. The number of sandwich canapes eaten after saline or CCK-8 infusion was recorded during three consecutive 10-min eating periods. Each subject served as his/her own control. The prior infusion of CCK-8 significantly decreased the consumption of sandwich canapes in the first eating period in both the control obese subjects and the subjects with obesity due to hypothalamic injury. Insertion of a gastric bubble did not enhance the satiety effect of CCK-8. These studies support the hypothesis that CCK produces satiety in a time-dependent manner that is not enhanced after the insertion of a gastric bubble but is operative in obese subjects with hypothalamic injury.

Cholecystokinin↗
PubMed1992

Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity.

The effect of mifepristone (RU 486), a blocker of type II glucocorticoid receptors on the development of obesity that follows the feeding of a high-fat (HF) diet to Osborne-Mendel (OM) rats, has been investigated. OM rats fed a HF diet gained more weight and had larger retroperitoneal and parametrial fat pads than OM rats fed a high-carbohydrate low-fat (LF) diet. RU 486 (30 mg.kg-1.day-1) for 14 days completely reversed the body weight gain and the increase in fat pad size of OM rats fed a HF diet. RU 486 had no effect on body weight of OM rats fed a LF diet, but did reduce fat pad weights. The data suggest that type II glucocorticoid receptor activity modulates body fat deposition and is essential for the development of obesity, although a minor role for progestin receptor activity cannot be ruled out.

Animals↗
PubMed1992

Differential inhibition of fat intake in two strains of rat by the peptide enterostatin.

The effect of enterostatin, the amino-terminal pentapeptide of pancreatic procolipase, on food intake was investigated in two strains of rat, the dietary fat-sensitive Osborne-Mendel (OM) rat and the dietary fat-resistant S5B/Pl rat. After an overnight fast, enterostatin inhibited intake of high-fat (HF) but not low-fat (LF) diets in OM rats, but had no effect in S5B/Pl rats. When fed a macronutrient three-choice diet, OM rats selected fat preferentially, whereas S5B/Pl rats selected carbohydrate. Enterostatin specifically inhibited the intake of fat in OM rats but not S5B/Pl rats fed a three-choice macronutrient diet. The activity of pancreatic colipase was increased in S5B/Pl rats on both HF and LF diets compared with OM rats. Pancreatic colipase activities were negatively related to the voluntary intake of fat on three-choice macronutrient diets. The data support the hypothesis that enterostatin may control the intake of dietary fat.

Animals↗
PubMed1992

Whole body insulin sensitivity in Osborne-Mendel and S 5B/Pl rats eating a low- or high-fat diet.

To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high-fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects.

The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal-weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10-12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min KG value (KGs), was much reduced in the evening (AM 2.98 +/- 0.45, PM 1.86 +/- 0.33 min-1, P less than 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 +/- 0.31 min-1), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 +/- 0.18 min-1, P greater than 0.40). The reduction in glucose tolerance in the normal-weight subjects was caused by diminished insulin sensitivity (parameter S1, AM 15.4 +/- 2.9, PM 10.2 +/- 1.9 x 10(-5) min-1/pM, P less than 0.01) and reduced beta-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 +/- 441, PM 1825 +/- 381 pM/10 min, P less than 0.05) and the potentiation slope (AM 462 +/- 68, PM 267 +/- 35 pM/mM, P less than 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 +/- 0.7, PM 4.9 +/- 1.0 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Fluoxetine treatment of the obese diabetic.

Fluoxetine, an inhibitor of serotonin re-uptake, has been shown to cause weight loss in humans and animals. In order to determine the effects in diabetic subjects, 48 male and female, obese, type 2 non-insulin dependent diabetics being treated with insulin were randomized to receive fluoxetine 60 mg or placebo once daily in double blind fashion for 24 weeks. In all subjects, this treatment was preceded by four weeks and followed by six weeks of single blind placebo washout treatment. Subjects performed daily home glucose monitoring and were given instruction in a 1200 kcal American Diabetes Association diet. Fluoxetine treated subjects who completed the trial (n = 16) lost more weight than placebo treated subjects (n = 20) (9.3 +/- 2.4 vs. 1.9 +/- 2.9 kg +/- s.e.m, P less than 0.05). Subjects in the fluoxetine group also showed a greater percentage decrease in insulin dose than those in the placebo group (46.9 +/- 7.6% vs. 19.3 +/- 7.6%, P less than 0.01). During active treatment, the change in serum glucose levels did not differ between the two groups, while glycohemoglobin fell more in fluoxetine treated subjects than in placebo treated subjects at two of four follow-up visits. These results suggest that fluoxetine may be of benefit in the treatment of obese patients with type 2 non-insulin dependent diabetes mellitus.

Adult↗
PubMed1992

A retrospective view of obesity.

To gain a perspective on 'obesity in the nineties' requires an understanding of where the field came from during the 1980s. Three main themes seem to characterize much of the research during the 1980s. First there was completion of development of multi-disciplinary treatment programmes utilizing the best behavioural modification, nutrition education, exercise and on occasion pharmacological adjuncts. Most characteristic of all was the widespread use of very low calorie diets which first appeared at the beginning of the decade and peaked at its end. The second major development of the 1980s was the recognition of the importance of fat distribution in addition to total fat as a risk factor for the consequences of obesity. Finally, the 1980s saw the development of serotonin agents and the initial studies with beta adrenergic agonists for the treatment of obesity based on the concepts of nutrient partitioning and reduced sympathetic activity. As we enter the 1990s, three additional themes appear to be in the ascendancy. The first will be the emphasis on molecular mechanisms as an explanation for the genetic diversity of obesity, including fat distribution. The second will be the focus on strategies for prevention of obesity. The third will be the development of newer and more innovative techniques for treating that obesity which we cannot prevent.

Adipose Tissue↗
PubMed1992

Obesity increases risk for diabetes.

The relationship of obesity to the development of diabetes has been reviewed. Older individuals are more obese and have more diabetes. Both the duration and magnitude of the obesity increase risk of diabetes. Family history of diabetes mellitus is also important in whether obesity leads to diabetes. Abdominal body fat increases the risk of diabetes. These factors help in understanding the reasons why obesity poses such a high risk for developing diabetes mellitus.

Blood Glucose↗