Letters to the editor: an editorial.
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Correspondence as Topic↗
Biomedical subjects
G A Bray
Publications and source records attributed to G A Bray.
Amphetamine: the Janus of treatment for obesity.
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Amphetamine↗
What's in a name? Mr. Dickens' "Pickwickian" fat boy syndrome.
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England↗
Harvey Cushing and the neuroendocrinology of obesity.
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Cushing Syndrome↗
Vagal-central nervous system interactions modulate the feeding response to peripheral enterostatin.
Enterostatin selectively inhibits the intake of dietary fat after both peripheral and central administration. We have investigated the role of the hepatic vagus nerve in modulating the peripheral response to enterostatin in Sprague-Dawley rats adapted to a high fat (HF) diet. Intraperitoneal (ip) enterostatin reduced intake of HF diet after overnight starvation. This response was abolished by selective vagal hepatic branch transection. Immunohistochemical techniques were used to identify the location of Fos protein in brain nuclei after ip enterostatin. Fos protein was evident in the nucleus tractus solitarius (NTS), parabrachial, paraventricular and supraoptic nuclei. The pattern of expression of Fos-like immunoreactivity differed from that induced by the lipoprivic agent beta-mercaptoacetate. Transection of the hepatic vagus blocked the central Fos responses to ip enterostatin. We conclude that afferent hepatic vagal nerve activity is required for the feeding response to peripheral enterostatin.
Animals↗
The inheritance of corpulence.
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Biometry↗
Extracellular hypothalamic monoamines measured by in vivo microdialysis in a rat model of dietary fat-induced obesity.
We tested two hypotheses about monoamine neurotransmitters in two strains of rats that differ in their sensitivity to obesity when eating a high-fat diet; 1) that the concentrations of norepinephrine and serotonin and of their metabolites differ in the extracellular fluid of the ventromedial hypothalamus of conscious, unrestrained Osborne-Mendel and S 5B/Pl rats, and 2) that these monoamines are altered differently between strains by a high-fat diet. The monoamines were measured by HPLC in dialysate collected by in vivo microdialysis in rats eating a semisynthetic low-fat diet (10% of kcal as fat) and again after either two or seven days of eating a high-fat diet (56% of kcal as fat). Norepinephrine, serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) were lower in Osborne-Mendel rats than in S 5B/Pl rats eating the low-fat diet. Norepinephrine and serotonin both increased in Osborne-Mendel rats with the onset of the high-fat diet so that Osborne-Mendel and S 5B/Pl rats no longer differed in these neurotransmitters. By day 7 of high-fat feeding, the concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-HIAA and the 5-HIAA/5-HT ratio rose in both strains. Ambient extracellular monoamines in the medial hypothalamus are lower in Osborne-Mendel rats than in S 5B/Pl rats and the response of these catecholamines to dietary fat was greater in Osborne-Mendel rats than in S 5B/Pl rats.
Animals↗
Lavoisier and scientific revolution: the oxygen theory displaces air, fire, earth, and water.
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Chemistry↗
Validity and reliability of reported dietary intake data.
OBJECTIVE: To compare two training techniques for validity and reliability of dietary instruments and the measurement of total energy expenditure (TEE) to determine whether technique could influence the accuracy of food portion estimates. DESIGN: Adult women were randomized into a control group and an experimental group for comparison of training technique. SETTING: University and research center. SUBJECTS: Five hundred women were screened using the Three-Factor Eating Questionnaire to identify restrained eaters or disinhibitors. Other criteria for selection included good health; absence of thyroid, respiratory, or other diseases; normal menstrual cycles; between the ages of 18 and 50 years. Forty-nine were recruited, with an attrition rate of 10% for a total sample of 44 subjects. INTERVENTION: The control group (n = 26) was trained with food models and the experimental group (n = 18) was trained with a combination of food models and life-sized food photographs. All subjects completed two 24-hour recalls and 14 consecutive days of food records. TEE was measured by the doubly-labeled water method. MAIN OUTCOME MEASURES: Training would improve the accuracy of food portion estimates. STATISTICAL ANALYSES PERFORMED: Analysis of variance, the paired t test, Pearson's correlation coefficient, and Wilcoxon's ranking test. RESULTS: The mean reported intake between instruments was found to be reliable; however, the comparison with TEE was underreported by 21.4% and was thus nonvalid. Training technique made no difference in validity or reliability. Both training techniques improved the accuracy of food portion estimates; however, improvement was enhanced with food photographs. APPLICATIONS/CONCLUSION: The findings indicate that training can improve food portion estimates, and dietary instruments may provide reliable but nonvalid results.
Adult↗
Effects of clenbuterol, a beta 2-adrenoceptor agonist, on macronutrient selection in rats.
In these studies, clenbuterol, a beta 2-adrenergic agonist, was injected into male rats and the intake of a three-choice macronutrient diet was measured. The intakes of fat and protein were selectively inhibited by clenbuterol in both overnight-fasted and freely fed rats. There was no effect of clenbuterol on carbohydrate intake. Prior administration of nadolol, a beta-adrenergic antagonist, which does not easily pass the blood-brain barrier, completely antagonized the anorectic effect of clenbuterol. However, section of the hepatic branch of the vagus nerve did not abolish the nadolol effect. These results suggest that the anorectic effect of clenbuterol is mediated by peripheral beta 2-adrenergic receptors rather than central beta 2-adrenoceptors, and is not related to information transmitted from the liver via the vagus nerve.
Afferent Pathways↗
Structural requirements for the biological activity of enterostatin.
A series of enterostatin analogues were tested to investigate the minimal structure required for activity to suppress the intake of high-fat (HF) diets. The dose-response curve to intracerebroventricular (ICV) enterostatin was U-shaped (maximal inhibition at 1 nmol). Removal or modification of the N-terminal valine from enterostatin (Val-Pro-Asp-Pro-Arg) abolished activity, as did C-terminal amidation. The tripeptide (Pro-Asp-Pro) and the cyclo-diketopiperazine cyclo-Asp-Pro retained activity whereas the linear Asp-Pro dipeptide was inactive. In rats adapted to a three-choice macronutrient diet, cyclo-Asp-Pro specifically inhibited fat intake and had near maximal inhibition (50%) at the 0.03 nmol dose. The enterostatin inhibitory effect on fat intake may reside in the cyclo-diketopiperazine molecule, cyclo-Asp-Pro.
Amino Acid Sequence↗
Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity.
Acute central administration of galanin has been reported to increase fat consumption. These experiments were designed to test the hypothesis that repeated injections of galanin would elicit hyperphagia and weight gain and that this response would depend on the available diet. Male Sprague-Dawley rats were fed high (56% energy) or low (10% energy) fat diets. Galanin (300 pmol) or saline vehicle was injected into the third ventricle twice daily for 7 days and three times daily for another 6 days. On both the high-carbohydrate and high-fat diets, twice daily galanin increased daytime food intake, but there was a compensatory decrease in nighttime intake. The addition of a third, nighttime injection of galanin was ineffective in producing an increase in total 24-h intake. There was no significant increase in body weight during galanin treatment in rats eating either diet although animals eating the high-fat diet gained more weight as reflected by a significant increase in epididymal fat pad weight. Galanin treatment had no effects on serum insulin, glucose or corticosterone concentrations, measured at the end of the experiment. However, animals fed the high-fat diet had significantly higher insulin concentrations at the time of sacrifice. Although repeated central infusions of galanin reliably stimulated daytime intake of both diets, they failed to increase total daily energy intake or body weight.
Animals↗
Relationship between food intake and metabolic rate in rats treated with beta-adrenoceptor agonists.
The purpose of the present experiment was to clarify the interaction between food intake and activity of the thermogenic component of the sympathetic nervous system by studying the dose response relationships of typical beta 1-, beta 2-, and beta 3-adrenoceptor agonists on oxygen consumption and food intake. The data showed that the ED50 for the effects of Dobutamine (beta 1), Clenbuterol (beta 2) and ICI D7114 (beta 3) agonists on food intake were 8.9, 0.041 and > 1.1 mumol/kg respectively whereas the ED50 values for stimulation of metabolic rate were 7.1, 1.3 and 0.11 mumole/kg respectively. The marked differences in ED50 values for suppression of food intake and stimulation of metabolic rate for both clenbuterol and ICI D7114 suggest that the regulation of feeding and of metabolic rate in response to these agonists are independent of each other. The experiments also identified that Clenbuterol activated a very sensitive beta 2-adrenergic system for the regulation of feeding behavior.
Adrenergic beta-Agonists↗
Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monoamine metabolism.
Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monamine metabolism. The central hypothesis underlying this study is that there is a reciprocal relationship between food intake and sympathetic activity to IBAT. This hypothesis was tested by using intrahypothalamic microinjections of glucagon, a peptide that has been reported to decrease food intake. Sympathetic nerve activity to interscapular brown adipose tissue (IBAT) was measured as electrophysiological discharges of sympathetic nerves to IBAT. The microinjection of glucagon into the lateral hypothalamus (LH) increased sympathetic nerve activity by +103.8 +/- 35.0% (mean +/- S.E.M.) from pre-injection basal level by 30 min after injection. There was a gradual return to baseline. Micro-injection of glucagon into the LH depressed food intake. Monoamine metabolism was measured by using a microdialysis probe attached to a guide cannula for microinjection of glucagon into the LH. After microinjection of glucagon, the dialysates were collected over 30 min intervals and assayed for norepinephrine (NE), serotonin (5-HT), dopamine (DA) and their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG); 5-hydroxyindole-3-acetic acid (5-HIAA); and 3,4-dihydroxyphenylacetic acid (DOPAC). Glucagon suppressed both NE and MHPG concentrations in the lateral hypothalamus (LH), and the concentration of DOPAC was also decreased. There was no change of 5-HT concentration but 5-HIAA levels were reduced by glucagon treatment. These data show that glucagon injected in the LH stimulates sympathetic activity and suggest that this may have occurred by suppression of norepinephrine, dopamine and serotonin turnover in the LH of freely moving rats. These data support the hypothesis of a reciprocal relationship between food intake and sympathetic activity.
Adipose Tissue, Brown↗
Use and abuse of appetite-suppressant drugs in the treatment of obesity.
Most of the available appetite-suppressant drugs act on noradrenergic and possibly dopaminergic receptors to produce satiety. A smaller number increase excess neuronal serotonin levels by blocking serotonin reuptake or by increasing its release. All these drugs produce significantly greater weight loss than does placebo in most studies. Abuse is a problem with amphetamine, methamphetamine, and benzphetamine, whereas other drugs have minimal or no potential for abuse. Weight loss can be sustained for up to 36 months. Net weight loss, compared with placebo, ranges from 2 to 10 kg, and weight regain after terminating drug treatment proves that drugs do not work when not taken. The stigma of obesity, the public opprobrium toward obese persons, and regulatory rigidity have led to unjustified distrust in the potential of drug treatment for obesity.
Appetite Depressants↗
Effects of castration, estrogen replacement and estrus cycle on monoamine metabolism in the nucleus accumbens, measured by microdialysis.
Changes in monoamine concentration in the nucleus accumbens were measured by microdialysis during the estrus cycle of intact females rats as well as untreated ovariectomized rats and ovariectomized rats treated with estrogen and progesterone. Norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG) dopamine (DA), 3,4-dihydroxyphenylacetic acid, (DOPAC), serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) were measured by high performance liquid chromatography. The ratio of MHPG to NE and DOPAC to DA were significantly increased during proestrus when compared to other phases of the estrus cycle. The ratio of 5-HIAA:5-HT, however, was significantly reduced during proestrus. Treatment of ovariectomized rats with estradiol at either 1 microgram/day or 10 micrograms/day significantly increased the ratio of MHPG:NE and DOPAC:DA. In contrast, the ratio of 5-HIAA:5-HT decreased significantly. Progesterone had no significant effect on the concentrations of 5-HT or 5-HIAA, but attenuated the effect of estrogen on the ratio of MHPG:NE and similarly reduced the ratio of DOPAC:DA. These studies are consistent with the hypothesis that estrogens are associated with enhanced metabolism of NE and decreased metabolism of 5-HT and dopamine in the nucleus accumbens of freely moving rats.
Animals↗
Procolipase mRNA: tissue localization and effects of diet and adrenalectomy.
Northern blot analysis has identified procolipase mRNA in rat pancreas, stomach and duodenum. Pancreatic colipase mRNA was increased by high-fat diets. Adrenalectomy increased pancreatic procolipase mRNA, an effect enhanced by high-fat diets. The results suggest that colipase is not unique to the pancreas and that diet and glucocorticoids interact in regulating the transcription of its gene.
Actins↗