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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 73 records · Page 4Linked to original sources
PubMed1999

Long-term calorie restriction reduces energy expenditure in aging monkeys.

Calorie restriction to produce stable long-term adult body weight for approximately 10 years prevents obesity and diabetes in middle-aged rhesus monkeys. To determine whether this dietary regimen also alters energy metabolism, the doubly labeled water method was used to measure total daily energy expenditure. Six adult male rhesus monkeys, which had been calorie-restricted for more than 10 years, were compared to 8 control adult monkeys, which had been fed ad libitum for their entire lives. The calorie-restricted monkeys weighed less than the ad-libitum fed monkeys and had a lower lean body mass and lower fat mass. Total daily energy expenditure was lower in the calorie-restricted than in the ad-libitum fed monkeys, even when corrected for differences in body size using body weight (563 +/- 64 vs 780 +/- 53 kcal/d; p < .04), surface area (547 +/- 67 vs 793 +/- 56 kcal/d; p < .05), or lean body mass (535 +/- 66 vs 801 +/- 54 kcal/d; p < .02) as covariates. Thyroxine (T4) was reduced and the free thyroxine index was suggestively lower in the calorie-restricted monkeys whereas triiodothyronine (T3) was not significantly different. Activity in calorie-restricted monkeys was similar to that of a weight-matched younger adult comparison group. We conclude that the process of preventing obesity by long-term caloric restriction causes a significant and sustained long-term reduction in energy expenditure, even when corrected for lean body mass.

Adipose Tissue↗
PubMed1999

Low-dose T(3) improves the bed rest model of simulated weightlessness in men and women.

This study tested the hypothesis that low-dose 3,5, 3'-triiodothyronine (T(3)) administration during prolonged bed rest improves the ground-based model of spaceflight. Nine men (36.4 +/- 1. 3 yr) and five women (34.2 +/- 2.1 yr) were studied. After a 5-day inpatient baseline period, subjects were placed at total bed rest with 6 degrees head-down tilt for 28 days followed by 5-day recovery. Fifty micrograms per day of T(3) (n = 8) or placebo (n = 6) were given during bed rest. Serum T(3) concentrations increased twofold, whereas thyroid-stimulating hormone was suppressed in treated subjects. T(3)-treated subjects showed significantly greater negative nitrogen balance and lost more weight (P = 0.02) and lean mass (P < 0.0001) than placebo subjects. Protein breakdown (whole body [(13)C]leucine kinetics) increased 31% in the T(3) group but only 8% in the placebo group. T(3)-treated women experienced greater changes in leucine turnover than men, despite equivalent weight loss. Insulin sensitivity fell by 50% during bed rest in all subjects (P = 0.005), but growth hormone release and insulin release were largely unaffected. In conclusion, addition of low-dose T(3) to the bed rest model of muscle unloading improves the ground-based simulation of spaceflight and unmasks several important gender differences.

Adult↗
PubMed1999

Activation of hypothalamic serotonin receptors reduced intake of dietary fat and protein but not carbohydrate.

Systemic treatment with dexfenfluramine (dF), fluoxetine, or serotonin (5-hydroxytryptamine, 5-HT) recently was shown to suppress fat and occasionally protein but not carbohydrate intake in rats when a macronutrient selection paradigm was employed. These reports contrast with the prevailing literature, which for the past decade has described a role for serotonin neurotransmission in the modification of dietary carbohydrate consumption. To test the hypothesis that the suppression of fat selection and/or consumption by systemic serotonin agonists involves stimulation of central 5-HT receptors, a series of experiments was performed in nondeprived rats. In experiment 1, third cerebroventricular (3V) infusion of the nonselective 5-HT antagonist metergoline prevented the reduction in fat but not carbohydrate feeding caused by systemic dF. Furthermore, 3V metergoline alone increased fat intake. In experiments 2 and 3, 3V infusion of 5-HT(1B/2C) receptor agonists D-norfenfluramine (DNF) or quipazine inhibited fat intake exclusively. Next, the infusion of DNF or 5-HT into the region of the paraventricular nucleus (PVN) reduced both fat and protein intake (experiments 4 and 5). Finally, in experiment 6, when rats were grouped by baseline diet preference, 5-HT infused into the PVN led to a dose-related decrease in fat intake in both carbohydrate- and fat-preferring rats. In contrast, there were no dose effects of 5-HT on carbohydrate or protein intake in either preference group. However, in fat-preferring rats, the highest dose of 5-HT reduced intake of all three macronutrient diets. These results demonstrate a selective effect of exogenous serotonergic drugs in the hypothalamus to reduce fat rather than carbohydrate intake and suggest that higher baseline fat intake enhances responsivity to serotonergic drugs.

Animals↗
PubMed1999

Therapeutic controversy: Obesity--a modern-day epidemic.

While the hyperleptinemia of obesity is likely to be associated with the metabolic complications of obesity/hyperinsulinemia/insulin resistance, it is not associated with diabetes, with the relative hypercortisolism of upper body obesity, with hypertension in women, (it is in men), or with dyslipidemia. Overall, the correlations between leptin and the metabolic diseases associated with obesity are weak. The equivocal results of an association of leptin with components of the metabolic syndrome make it unlikely that leptin affects these directly. (On the other hand, these correlations, when found, preclude any causal relationship between leptin and metabolic diseases.) There are experimental data showing a definite role for insulin and glucocorticoids in the regulation of leptin, and of leptin in the regulation of insulin. More data are required on the effects of leptin, but it is likely that leptin will not be a major link between obesity and the metabolic syndrome. Certainly, however, when leptin is available for clinical use, its effect on different aspects of the metabolic syndrome will be worth studying.

Energy Metabolism↗
PubMed1999

Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest.

Decrements in muscle strength as a result of prolonged bed rest are well defined, but little is known about potential countermeasures for preventing loss of strength under this condition. The purpose of this study was to determine whether testosterone administration would preserve protein balance and muscle strength during prolonged bed rest. Ten healthy men (age, 36 +/- 2 yr; height, 177.2 +/- 3.4 cm; weight, 80.5 +/- 3.9 kg; mean +/- SE) were admitted to our in-patient metabolic unit. After a 1-week ambulatory run-in period, each subject was confined to bed for 28 days at 6 degree head-down tilt while receiving a daily oral dose of T3 (50 microg/day). During the bed rest/T3 period, six of the men were randomized to receive testosterone enanthate by i.m. injection (T; 200 mg/week) while four received placebo in a double blind fashion. Nitrogen balance was determined throughout, and whole body [13C]leucine kinetics were assessed at baseline and on day 26 of bed rest. Before bed rest and on the third day of reambulation, the muscle strength of the knee extensors and flexors and shoulder extensors and flexors was determined at 60 degrees/s on a Cybex isokinetic dynamometer. Despite improved [13C]leucine kinetics and maintenance of nitrogen balance and lean body mass in T-treated subjects, little preservation of muscle strength, particularly in the knee extensors, was noted. Muscle strength [reported as the best work repetition in foot-pounds (FtLb)] for right knee extensors declined (P = 0.011) similarly in both groups; from 165 +/- 15 to 126 +/- 18 FtLb in T-treated men and from 179 +/- 22 to 149 +/- 13 FtLb in placebo-treated men. Overall, there was less of a decline in extension and flexion strength of the shoulder compared to the knee, with no benefit from T. These results suggest that in the absence of daily ambulatory activity, T administration will not increase or, in the case of this bed rest model, preserve muscle strength.

Adult↗
PubMed1999

Uses and misuses of the new pharmacotherapy of obesity.

The worldwide epidemic of obesity has made the development of effective treatment ever more urgent. Appropriate use of medication for the treatment of obesity may benefit patients at risk for developing diabetes, hypertension, coronary artery disease, osteoarthritis or gall bladder disease. In addition, with the appearance of very safe medications, short-term treatment for the relief of the stigma associated with obesity may also be valuable. The currently available medications for obesity work either by reducing fat digestion or by acting on receptor systems in the brain. Both have potential side-effects, but may be useful alone or in combination. The expansion of knowledge about the control of obesity offers the hope that many new agents will become available over the next decade.

Appetite Depressants↗
PubMed1999

Nutrition and obesity: prevention and treatment.

The increased risk of morbidity and mortality from obesity, central body fat, and weight gain, and the beneficial effects of weight reduction argue that the cost associated with obesity could be beneficially affected by prevention of weight gain or induction of weight loss. Genetic, metabolic, and demographic predictors of weight gain have been identified that allow selection of high-risk individuals. Among the metabolic predictors are a low metabolic rate, insulin sensitivity, and a high respiratory quotient. Demographic predictors include current smokers, certain dieting behaviors, lower socio-economic class, a low level of education, use of contraceptives, status post-partum, and rapid weight gain in childhood. Several studies suggest that weight gain can be prevented. Targets for such strategies might be high-risk families, current smokers, those who are planning to stop smoking, and those with a low metabolic rate. For those who fail primary prevention, treatment may be appropriate. The greater the degree of excess weight, the greater the risk and the more appropriate treatment becomes to reduce body weight.

Body Mass Index↗
PubMed1998

Dietary fat preferences are inversely correlated with peripheral gustatory fatty acid sensitivity.

We previously demonstrated that taste receptor cells (TRCs) respond to cis-polyunsaturated fatty acids (PUFAs) through an inhibition of delayed rectifying K channels (KDR), which may represent the transduction mechanism for dietary fat. To determine if there is a link between the sensitivity of fungiform TRCs to PUFAs and dietary fat preferences, we compared the PUFA-sensitivity of TRCs using patch clamp techniques from Osborne-Mendel (O-M) and S5B/Pl rats, which display dietary preferences for fat over carbohydrate and carbohydrate over fat, respectively. In isolated TRCs, the PUFAs, linoleic (C18:2), linolenic (C18:3) and arachidonic acid (C20:4) inhibit KDR in a concentration-dependent manner in both strains, while the unsaturated lauric acid (C12:0) was ineffective. KDR from TRCs of S5B/Pl rats were significantly more sensitive to inhibition by all three PUFAs (10 microM) than were TRCs from O-M rats. We are currently investigating whether this differential responsiveness is due to (i) the relative affinity of the interaction between cis-PUFAs and the delayed rectifying K channels or (ii) the relative density of delayed rectifying K channels in the two rat strains. Whatever the mechanism, these data suggest an inverse correlation between peripheral gustatory sensitivity to PUFAs and the dietary preference for fat. This finding may provide insight into the mechanism for sensing dietary fat that allows the S5B rats to reduce fat intake on a high-fat diet and avoid the obesity which results when O-M rats eat a high-fat diet.

Animals↗
PubMed1998

A beta-3 adrenergic agonist (BRL-37,344) decreases food intake.

This study evaluated the effect of peripheral injections of a beta3 adrenergic agonist, BRL-37,344 on food intake and whether this inhibition could be blocked by a nonspecific beta-adrenergic antagonist, propranolol, given peripherally or into the central nervous system. When BRL-37,344 was injected intraperitoneally (i.p.) into lean and obese Zucker rats, food intake was decreased. The reduction of food intake by BRL-37,344 was attenuated when propranolol was administered i.p. prior to giving the beta adrenergic agonist. When propranolol was administered into the third cerebral ventricle, it increased food intake in lean rats, but not the fatty rats. Propranolol administered into the third cerebral ventricle attenuated the effect on food intake of i.p. injection of BRL-37,344. These studies support the hypothesis that there are peripheral beta-3 adrenergic receptors that can reduce food intake and that there are central beta2 or beta3 adrenergic receptors that mediate the peripheral effect of the beta3 agonist.

Adrenergic beta-Agonists↗
PubMed1998

Perception of sweetness intensity determines women's hedonic and other perceptual responsiveness to chocolate food.

This study tested 63 women for hedonic and other perceptual responsiveness to a chocolate food. Subjects tasted four chocolate puddings varying in sugar (high and low) and fat (high and low) content and rated them for pleasantness, caloric density, fillingness and flavor intensities. Results emphasised the importance of sweetness intensity in determining women's responses to the chocolate puddings. Women's perception of sweetness intensity was accurate to sugar content and results consistently indicated that their hedonic responses to the chocolate puddings were based on the perceived sweetness. Women's perception of the caloric density of the puddings was based on their perception of the fat content of the puddings; however, interpretation of that finding must be qualified because the subjects' perception of fat content was inaccurate. The women's perception of sweetness intensity accounted for 31% of the variability in fat perception. Women's perception of the intensity of chocolate flavor was also significantly associated with perceived sweetness of the puddings. These data suggest that the women's accurate perception of the sugar content of the chocolate puddings played a primary role in determining their hedonic and other perceptual responses.

Adult↗
PubMed1998

Preferential fat intake increases adiposity but not body weight in Sprague-Dawley rats.

It is not known whether an inherent preference for dietary fat promotes obesity in animals allowed to self-select the proportions of fat and carbohydrate consumed. To address this question, Sprague-Dawley rats were given a choice between two diets containing either 78% fat (by energy) or 78% carbohydrate; both diets were equicaloric for protein (22%). The entire study lasted 12 weeks. After an adaptation period, macronutrient preferences were determined by measuring 24 h intake of the two diets for 5 days; fat-preferring animals were classified as those that consumed greater than 60% of total energy from the fat/protein source, and carbohydrate-preferring rats as those that consumed less than 40%. Rats with intermediate macronutrient intakes were excluded. Initial body weight was not different between preference groups. Caloric intakes and body weights were then recorded at approximate weekly intervals, and fat depots were weighed at the time of sacrifice. Measures of energy intake and body weight did not differ between the two preference groups over time. In addition, baseline macronutrient preferences remained stable across the study period. Despite similar body weights, mean epididymal fat depot weight was significantly higher in fat-preferring rats than in carbohydrate-preferring rats (12.6 vs. 10.0 g); also, mean inguinal fat depot weight in fat-preferrers was greater although not reliably different compared to carbohydrate-preferring rats (12.9 vs. 10.9 g). Thus, the preferential intake of fat led to a greater deposition of both subcutaneous and visceral fat without an increase in body weight. These data lead us to conclude that the increased fat deposition was due primarily to the ingestion of fat rather than to excess caloric intake.

Adipose Tissue↗
PubMed1998

Association of dietary restraint and disinhibition with eating behavior, body mass, and hunger.

This study investigated the association of dietary restraint and disinhibition with self-reported and actual eating behavior, body mass, and hunger. A sample of 124 women were categorized into one of four groups based upon high and low scores on measures of Dietary Restraint and Disinhibition using the Three Factor Eating Questionnaire. Half of the participants in each group consumed a high sugar/high fat chocolate pudding as a dietary preload. All participants were given a meal comprised of a standard macaroni and beef product. The interaction of Dietary Restraint and Disinhibition was related to differences in body mass. The Dietary Restraint factor was related to self-reported pathological eating behavior and influenced both perceived hunger and subjective hunger ratings. However, actual eating behavior measured by calories consumed and rate of intake was unrelated to the Dietary Restraint factor. Disinhibition was associated with excessive eating, an increased rate of eating, self-reports of eating disorder symptomatology, and perceived hunger. Hence, actual eating behavior was significantly influenced by the ingestive motivational factor, Disinhibition, but not by the cognitive factor, Dietary Restraint. These data also suggest that the Disinhibition construct is measuring overeating rather than disinhibited eating which implies the disruption of Dietary Restraint.

Adolescent↗
PubMed1998

Assessment of energy intake underreporting by doubly labeled water and observations on reported nutrient intakes in children.

OBJECTIVE: To compare reported energy intake with energy expenditure using doubly labeled water (DLW). Additionally, we compared reported nutrient intakes of our subject population with national survey population data from the third National Health and Nutrition Examination Survey (NHANES III). DESIGN: This was a cross-sectional study of children, balanced by race and gender, primarily characterized by 4 body types: lean, obese, centrally fat, or peripherally fat. SUBJECTS/SETTING: Children (n=118; mean age=10 years) kept 8-day food records, with nutritionists recording weekday school lunch intakes. These subjects, assisted by their parents, recorded all breakfasts, dinners, snacks, and weekend lunches. STATISTICAL ANALYSES PERFORMED: Data were analyzed using least squares analysis of variance with the general linear models procedure. Tukey's test was used for multiple comparisons of predicted treatment means. RESULTS: Mean daily energy intake was underreported by 17% to 33% of energy expenditure. The tendency to underreport increased with age. Underreporting occurred in all groups and subgroups studied. Reported mean intakes of vitamin A, vitamin E, vitamin B-6, calcium, zinc, and copper were less than 70% of the Recommended Dietary Allowance (RDA) for African-American girls, whereas African-American boys reported similarly low intakes of copper. On average, white girls reported intakes less than 70% of the RDA for zinc and copper, whereas white boys reported low intakes of copper (60% of the RDA). Reported intakes in general were somewhat lower than those reported in NHANES III. APPLICATIONS/CONCLUSIONS: Dietetics professionals may modify the nutritional advice they give to patients/subjects based on food intake records and other data. For children, particularly, it is imperative that ethnic and gender differences be taken into consideration and that all foods eaten be accounted for as much as possible.

Black or African American↗
PubMed1998

Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity.

The Differential Display technique has been used to identify differences in mRNA expression in adipose tissue after the introduction of a high fat diet to two strains of rat (OM and S5B/PI) that differ in their susceptibility to develop obesity on this diet. The insulin receptor tyrosine kinase inhibitor protein (fetuin) was shown to be differentially expressed in OM but not S5B/PI rats. This circulating protein may play a role in the development of peripheral insulin resistance associated with high fat diets.

Animals↗
PubMed1998

Macronutrient selection following 2-deoxy-D-glucose and mercaptoacetate administration in rats.

Mercaptoacetate (MA) and 2-deoxy-D-glucose (2-DG), which block fatty acid oxidation and glucose utilization respectively, were injected in rats that were maintained on a macronutrient self-selection diet consisting of separate jars of carbohydrate, protein, and fat. Rats were divided into two groups based on their baseline preference for carbohydrate or fat. MA increased intake of carbohydrate and protein and decreased intake of fat regardless of the rats' baseline preference. 2-DG increased intake of carbohydrate in rats regardless of baseline preference. Protein and fat intakes were not changed after 2-DG administration. If fat was the only macronutrient source available, 2-DG treated rats consumed significantly more fat compared to the saline control, whereas MA treated rats did not. When protein was the only macronutrient source available, both 2-DG and MA treated rats increased protein intake. MA increases the intake of nutrients which can be utilized by peripheral tissues except fat, which is not being oxidized. 2-DG increases the intake of carbohydrate which may be necessary to overcome the central glucoprivation caused by this drug.

Animals↗