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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two experiments examined the possibility that mice rendered obese by systemic injection of goldthioglucose (GTG) possess altered endogenous levels of brain norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine or 5HT) and/or 5-hydroxyindoleacetic acid (5HIAA). In the first experiment, single-housed GTG-obese mice were found to have normal brain DA and 5HIAA but 14% less NE and 6% less 5HT than controls. This neurochemical profile was strikingly similar to that previously reported for rats rendered obese by ventromedial hypothalamic lesions (i.e., normal DA and 5HIAA, 19% less NE, 7% less 5HT). However, in the second experiment, equally obese GTG mice pair-housed with non-obese controls showed normal DA, 5HIAA, and NE but 9% more 5HT than controls. In other words, absolute levels of these brain substances were inconsistent with respect to obesity across experiments. On the other hand, when ratios of all possible combinations of these compounds were compared across experiments, only 5HT/NE ratios were consistently different (higher) in GTG mice. In addition, reliable inverse correlations were obtained between weight gain parameters and brain 5HT/NE or 5HIAA/NE ratios for GTG mice. These findings suggest that interactions between brain 5HT and NE neurons may contribute to the overeating and obesity which occur in mice after GTG administration.
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PMID:Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice. 36 Feb 29

A review of evidence indicates that experimentally induced changes in the activity of serotonin (5-hydroxytryptamine) systems are associated with pronounced changes in feeding behaviour. In general, treatments and procedures believed to lead to an increased availability of 5-HT in the synaptic cleft or which directly activate 5-HT receptors reduce food consumption, while procedures which either directly or indirectly decrease 5-HT receptor activation bring about the opposite effect. Interpretation of findings is hindered by methodological difficulties involved in the experimental manipulation of serotonin metabolism, by the lack of precise behavioural measures of feeding, and by the presence of large stores of serotonin outside the brain. However, available data favour the idea that serotonin systems play an inhibitory role in feeding, possibly in the mediation of satiety. This proposal has implications for further experimental investigations of the control of food intake, and for the aetiology and treatment of obesity.
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PMID:Is there a role for serotonin (5-hydroxytryptamine) in feeding? 36 84

The effects of intracerebroventricular (ICV) administration of 5-hydroxytryptamine creatinine sulphate complex (5-HT), 35-140 nmol, on food intake in genetically obese (ob/ob) and lean mice were investigated. 5-HT (70-140 nmol) decreased feeding in a dose-related manner on 1 h and 2 h postinjection measures. Intake in lean mice was reduced by over 70% of the control condition. Obese mice, however, demonstrated a reduced sensitivity to the anorectic effect of 5-HT, and reduced 1 h intake by only 40% of saline control. Although these results are consisted with a role for serotonin in the control of food intake in mice, the altered sensitivity of the ob/ob to serotonergic stimulation may result, in part, from an impaired satiety control mechanism in this mutant.
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PMID:Central injection of 5-hydroxytryptamine reduces food intake in obese and lean mice. 161 Oct 36

Genetically obese Zucker rats are hyperphagic, hyperinsulinemic and hyperlipemic. In order to investigate pathophysiological mechanisms underlying hyperphagia in these animals, monoamine metabolism and turnover were studied in discrete hypothalamic nuclei known to participate in the control of feeding behavior. Neurochemical studies in genetically obese Zucker rats and in their lean littermate controls were complemented by investigating feeding behavioral responses to the acute administration of clonidine (15 and 30 micrograms/kg i.p.), an alpha 2-adrenoceptor agonist, and to trifluoromethylphenylpiperazine (TFMPP; 1, 2 and 5 mg/kg s.c.), a putative serotonergic 5-hydroxytryptamine-1B receptor agonist. Obese Zucker rats had significantly lower concentrations of 5-hydroxyindoleacetic acid, the main deaminated metabolite of 5-hydroxytryptamine, in the nucleus paraventricularis (PVN) and in the nucleus ventromedialis (VMN), when compared to their lean littermate controls. The rate of accumulation of 5-hydroxytryptophan after decarboxylase inhibition was reduced in the PVN, nucleus supraopticus, nucleus periventricularis and nucleus suprachiasmaticus of the obese rats. No differences were observed in basal concentrations of norepinephrine, dopamine or 3,4-dihydroxyphenylacetic acid between obese and lean Zucker rats in the brain areas studied. However, the rate of accumulation of 3,4-dihydroxyphenylalanine was lower in the VMN and in the median eminence of the obese rats. The feeding behavioral tests showed significantly augmented hyperphagic responses to clonidine in obese Zucker rats. The anorexic effect of TFMPP was similar in both phenotypes. It is concluded that serotonergic activity is reduced in obese Zucker rats, particularly in the PVN, which plays a key role in the control of feeding behavior. The reduced serotonergic activity may be associated with enhanced alpha 2-adrenoceptor-mediated feeding responses in obese Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothalamic neurochemistry and feeding behavioral responses to clonidine, an alpha-2-agonist, and to trifluoromethylphenylpiperazine, a putative 5-hydroxytryptamine-1B agonist, in genetically obese Zucker rats. 198 Jul 23

Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of primary hypertension associated with obesity.
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PMID:Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women. 206 May 60

Dexfenfluramine, the dextrostereoisomer of fenfluramine, is a pure serotonin (5-hydroxytryptamine) agonist, apparently devoid of any additional antidopaminergic or sympathomimetic effects. The drug is approximately twice as effective as its racemic predecessor in reducing food intake in animals, and at a dose of 30 mg/day dexfenfluramine substantially modifies eating behaviour in man. Thus, a reduction in the motivation to eat and fewer snacking episodes were seen in volunteers treated with the drug, while total caloric and carbohydrate (but not protein) intakes were reduced in obese carbohydrate cravers. In clinical studies in obesity, dexfenfluramine combined with dietary support has produced mean weight reductions superior to those achieved with placebo over 3-month treatment periods. Importantly, the drug appears to maintain its weight-reducing effects for at least 12 months, without serious adverse effects. Dexfenfluramine appears to possess many of the properties of an 'ideal' pharmacotherapeutic agent for obesity. However, further long term clinical studies are required to confirm the promising efficacy and safety data obtained to date, and to further define the most appropriate indications for its use. Ideally, the drug should be used as adjunctive treatment in the clinical management of more severe cases of obesity, which are refractory to simpler supportive measures such as dietary or psychological counseling.
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PMID:Dexfenfluramine. Its place in weight control. 219 76

Obese persons are often reported to have marked cravings for simple carbohydrate-rich foods. Because of the proposed relationships between protein/carbohydrate selection, plasma tryptophan (TRP) to large neutral amino acids (LNAA) ratios, and brain 5-hydroxytryptamine (5-HT) neurotransmission, we examined the plasma TRP/LNAA ratios in four categories of obese subjects, before and 120 min after oral glucose tolerance test (GTT). Plasma TRP/LNAA ratios were reduced in obese, non-diabetics by 18%, the same extent as for older (approximately 52 yr old) nonobese subjects. In more advanced obesity, ie obesity associated either with glucose intolerance, hyperinsulinemia or hypoinsulinemia, plasma TRP/LNAA ratios were reduced by 25%. One hundred twenty minutes after a 100 g glucose load plasma TRP/LNAA had not been normalized. Based on animal data, these results suggest there may be diminished 5-HT neurotransmission in obese diabetics. The implications of these findings for the cravings of obese for carbohydrate-rich foods is discussed.
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PMID:Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans. 390 26

Sprague-Dawley (S-D) and Osborne-Mendel (O-M) rats were fed either a low-fat diet (5 percent corn oil) or high-fat diet (20 percent corn oil) for a six-week-period. Brainstem and duodenal levels of tryptophan, serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were not altered by dietary treatment in the O-M rats. On the other hand, the high-fat diet significantly decreased brainstem 5-HT levels in S-D rats. Brainstem and duodenal 5-HT levels were decreased in O-M rats as compared to S-D rats and this phenomenon is not altered by dietary treatment. It is suggested that the O-M rat may have a alteration in the 5-HT metabolic system and that such a defect may contribute to the development of obesity.
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PMID:The effect of a high-fat diet on brainstem and duodenal serotonin (5-HT) metabolism in Sprague-Dawley and Osborne-Mendel rats. 621 Feb 59

In this literature review, evidence is presented for the theory that the neurotransmitter, serotonin (5-hydroxytryptamine, 5HT), in medial hypothalamic centres is an important regulator for appetite and for the selection of major food constituents. High local levels of 5HT cause a reduction of appetite and a preference for protein, low levels the opposite. The main antagonistic system is noradrenergic. The drug d-fenfluramine mimics the effects of 5HT by releasing 5HT from serotoninergic nerve endings and inhibiting its neuronal re-uptake. Further experimental data prove that a high-carbohydrate, low-protein diet promotes uptake of serum tryptophan in the brain and its conversion into 5HT. Hence, this serotoninergic system may function as a self-regulatory mechanism. In patients with decreased peripheral insulin sensitivity, the system may be disturbed, causing overconsumption of carbohydrates. This is sometimes compulsive ("carbohydrate craving"). It may be presumed that in the treatment of obesity, in addition to the use of serotoninergic drugs, successes with reducing diets may be enhanced by including periods of high-carbohydrate, low-protein intake. It would be worthwhile to explore whether similar alimentary self-regulatory mechanisms of neurotransmitter function exist in other regulatory systems.
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PMID:Appetite regulation by serotoninergic mechanisms and effects of d-fenfluramine. 796 65

A number of drugs are capable of changing bodyweight as an adverse effect of their therapeutic action. Bodyweight gain is more of a problem than bodyweight loss. As bodyweight gain during drug treatment for any kind of disease may be the reflection of improvement of the disease itself, we will try to separate these effects from those due to drug-induced alterations of the mechanisms regulating bodyweight. Bodyweight gain may jeopardise patient compliance to the prescribed regimen and it may pose health risks. The body mass index (BMI) is determined by dividing bodyweight in kilograms by height in metres squared. A BMI of > or = 27 kg/m2 warrants therapeutic action; nutritional counselling and programmed physical exercise can be used as a basis. In general, if basic therapeutic measures are unsuccessful at controlling bodyweight gain then a change of drug might help. Finally, an anoretic drug may serve to support dietary measures. However, safety and efficacy has been demonstrated for only a few anorectic drugs when used as an adjunct to caloric restriction in the treatment of drug-induced obesity. Bodyweight is determined by complex mechanisms regulating energy balance. A number of neurotransmitter systems acting in several hypothalamic nuclei are pivotal to the regulation of body fat stores. Most drugs that are capable of changing bodyweight interfere with these neurotransmitter systems. The increment is dependent on the type and dose of the drug concerned. Some antidepressant drugs induce bodyweight gain, which may amount to 20 kg over several months of treatment. Monoamine oxidase inhibitors appear to cause less bodyweight change than tricyclic antidepressants. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors cause bodyweight loss instead of bodyweight gain. Lithium may cause large increases in bodyweight. Generally speaking, the bodyweight change induced by antipsychotics is more often of clinical significance than the bodyweight change associated with the use of antidepressants. Again, the changes of bodyweight are dependent upon the type and dose of the antipsychotic drug involved. Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. Anticonvulsants, especially valproic acid (sodium valproate) and carbamazepine, induce bodyweight gain in a considerable percentage of patients. Treatment with corticosteroids is associated with dose-dependent bodyweight gain in many patients. Corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases bodyweight. Finally, sulphonurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause bodyweight gain as well.
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PMID:Bodyweight change as an adverse effect of drug treatment. Mechanisms and management. 880 Jun 28


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