Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The methylester hydrochlorides of DL-p-chlorophenylalanine (PCPA), L-leucine and L-tryptophan were intraventricularly administered to rats. All compounds produced increased food intake compared to saline administration. PCPA and leucine administration significantly decreased serotonin levels by 15--18%, while no serotonin depletion occurred following tryptophan injections. The data suggest that intraventricular injections of large quantities of neutral amino acid methyl esters may cause hyperphagia in rats through non-serotonergic effects on brain function.
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PMID:Hyperphagia following intraventricular p-chlorophenylalanine-, leucine- or tryptophan-methyl esters: lack of correlation with whole brain serotonin levels. 15 93

Effects of histidine or methionine imbalance and dietary levels (3-50%) of casein on food intake and preference of young, adult, and diabetic (2.5 month old) rats were examined. Depressions in food intake and growth caused by ingestion of the imbalanced diet were greatest in young rats and least or absent in diabetic rats. Alloxan diabetes induced hyperphagia and elevated concentrations of plasma branched-chain amino acids and decreased concentrations of tryptophan and tyrosine. The diabetic rats fed the imbalanced diet for 9 days had a higher concentration of the limiting amino acid in the plasma than the adult normal rats fed the same diet. The diabetic rats preferred the imbalanced diet over a protein-free diet when they were fed these diets concurrently. Ingestion of the imbalanced diet by normal rats caused greater changes in plasma and brain amino acid patterns than did the protein-free diet. Unlike the diabetic rats, the normal rats, especially the young rats, strongly preferred the protein-free diet over the imbalanced diet. The normal rats also preferred a 10% casein diet supplemented with L-methionine over a low or high casein diet. It seemed that young rats were able to select a protein diet that supported maximal growth when proportions of dietary amino acids were balanced. It also seemed that the susceptibility of the rats to amino acid imbalance varied directly with the status of overall protein synthesis of the animals.
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PMID:Effects of amino acid imbalance and protein content of diets on food intake and preference of young, adult, and diabetic rats. 119 6

Feeding or food withdrawal can affect the supply of tryptophan to the brain and hence (in some circumstances) 5-HT synthesis therein. Also fenfluramine which releases 5-HT to postsynaptic receptors suppresses appetite and there are reports that tryptophan can have a similar effect. Furthermore, feeding is reported to release hypothalamic 5-HT. Therefore 5-HT could have a role in the normal termination of feeding and perhaps also in disorders of appetite. The recognition of various 5-HT receptor subtypes has stimulated research in this area. We have now investigated the involvement of the subtypes in the pharmacological control of feeding. Thus, 5-HT1A agonists (8-OH-DPAT, buspirone, gepirone etc.) stimulate intake in freely feeding rats, probably by activating autoreceptors on the cell bodies of 5-HT neurons so that 5-HT release at terminals is decreased. The hyperphagia is not explicable by increased activity or gnawing and is strikingly manifest against carbohydrate in carbohydrate vs. protein choice experiments. Feeding in previously food deprived rats is decreased by the 5-HT agonists RU 24969, 1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl) phenyl]piperazine (TFMPP). Effects of antagonists suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors only while mCPP and TFMPP induce hypophagia at 5-HT1C sites, though this effect also requires 5-HT1B receptors for its expression. Responsible sites occur in the paraventricular nucleus of the hypothalamus as infusing either RU 24969 or TFMPP therein causes hypophagia. On systemic injection, the hypophagic drugs are particularly active in female rats, an effect of conceivable relevance to human anorexic illness.
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PMID:Effects of tryptophan and of 5-hydroxytryptamine receptor subtype agonists on feeding. 183 83

Feeding or food withdrawal can affect the supply of tryptophan to the brain and hence (in some circumstances) 5-HT synthesis therein. Also fenfluramine which releases 5-HT to postsynaptic receptors suppresses appetite, and there are reports that tryptophan can have a similar effect. Furthermore, feeding is reported to release hypothalamic 5-HT. Therefore 5-HT could have a role in the normal termination of feeding and perhaps also in disorders of appetite. The recognition of various 5-HT receptor subtypes has stimulated research in this area. We have now investigated the involvement of the subtypes in the pharmacological control of feeding. Thus, 5-HT1A agonists (8-OHDPAT, buspirone, gepirone, etc.) stimulate intake in freely feeding rats, probably by activating autoreceptors on the cell bodies of 5-HT neurons so that 5-HT release at terminals is decreased. The hyperphagia is not explicable by increased activity or gnawing and is strikingly manifest against carbohydrate in carbohydrate vs. protein choice experiments. Feeding in previously food-deprived rats is decreased by the 5-HT agonists RU 24969, 1-(3-chlorophenyl) piperazine (mCPP) and 1-(3-trifluoromethyl) phenyl) piperazine (TFMPP). Effects of antagonists on these properties suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors only, while mCPP and TFMPP induce hypophagia at 5-HT1C sites, though this effect also requires 5-HT1B receptors for its expression. Responsible sites occur in the paraventricular nucleus of the hypothalamus as infusing either RU 24969 or TFMPP therein causes hypophagia. On systemic injection, the hypophagic drugs are particularly active in female rats, an effect of conceivable relevance to human anorexic illness.
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PMID:Serotonin and appetite. 225 31

The effect of short-term undereating (4.2 MJ [1000 kcal] for 4 d) followed by overeating (12.6 MJ [3000 kcal] for 2 d) on fasting and 2-h postprandial serum glucose, insulin, and neutral amino acids and on urinary free and total norepinephrine and dopamine excretion was studied in 12 normal women. Protein and sodium intake was constant throughout the study. Serum glucose concentration was not affected by diet but the serum total neutral amino acids (ie, sum of valine, leucine, isoleucine, and phenylalanine) tended to increase during undereating and decrease during overeating. Serum tryptophan concentration, relative to the remaining neutral amino acids, was consequently lower during undereating than overeating. The postprandial increase in serum insulin level was greater during overeating than undereating. Urinary free norepinephrine and total dopamine levels were also increased during overeating, suggesting both sympathetic and dopaminergic activation during overeating after undereating.
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PMID:Short-term changes in energy intake and serum insulin, neutral amino acids, and urinary catecholamine excretion in women. 328 94

Experimental manipulations of 5-HT by central or peripheral procedures produce clear effects on food intake. Interpretation of these effects can be improved by monitoring changes in the behavioural structure of feeding and by designing experiments which adjust the contextual and temporal dimensions of feeding. Experimental techniques include micro-analysis of behaviour, macro-analysis of meal patterns, dietary self-selection of macro-nutrients, analysis of appetite and satiety sequences, appetitive and consummatory aspects of instrumental performance and dietary-induced hyperphagia. Using these procedures in conjunction with various pharmacological treatments including the administration of tryptophan, 5-hydroxy-tryptophan, 5-HT, re-uptake blockers, synaptic releasers, synthesis blockers, receptor blockers and others it has been demonstrated that 5-HT manipulations give rise to a specific constellation of changes in feeding parameters. The most prominent changes following peripheral or central (paraventricular nucleus) injections are a reduction in meal size and a curtailment of eating rate. These changes can be distinguished from those induced by other pharmacological treatments and are consistent with a modulation of the process of satiation and the state of satiety. Changes in feeding induced by 5-HT manipulations are not secondary to non-specific behavioural alterations.
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PMID:Serotonin manipulations and the structure of feeding behaviour. 352 61

Liver blood flow and exchange of oxygen, glucose, lactate, and amino acids were measured in pigs at the same time as the peripheral arteriovenous (A-V) difference of these substances was determined. Four groups of animals were studied; they were normal postabsorptive, septic fasted, and septic infused either with complete parenteral nutrition (4.25% mixed amino acid solution with 25% glucose) or an isocaloric solution of 1.8% leucine with glucose. Sepsis in the pig caused a rise in arterial concentration of all essential amino acids except tryptophan and a decrease of most of the others. The liver uptake of the sum of all amino acids rose from nonsignificant values to 26.03 mumol/min/kg at the same time as the peripheral A-V difference changed from +20.4 to -678.0 mumol/l. Hyperalimentation increased arterial amino acid concentration, whereas peripheral A-V difference decreased to -132.3 mumol/l. The total liver uptake of amino acids was 24.80 mumol/min/kg but with a higher proportion of essential amino acids than in the fasted septic state suggesting increased liver protein synthesis. When leucine and glucose were infused the peripheral A-V difference of the sum of all amino acids was only -45.6 mumol/l indicating an almost complete cessation of muscle proteolysis. The arterial plasma concentration of all amino acids except leucine, glutamine, and glutamate were markedly reduced. Although hepatic clearance rate of amino acids fell only slightly, due to the low plasma concentrations, the liver uptake decreased substantially to 7.37 mumol/min/kg suggesting a decreased liver protein synthesis which could be deleterious in the presence of sepsis.
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PMID:The effects of hyperalimentation and infused leucine on the amino acid metabolism in sepsis: an experimental study in vivo. 678 84

Young female obese (ob/ob) and lean mice were fed a single diet containing 10 or 20% casein or were allowed to self-select from two diets containing 10 and 50, 20 and 60, or 30 and 70% casein for 3 weeks. Obese and lean mice offered a choice of two diets varying in protein-consumed 36% and 32%, respectively, of energy from protein. Although both obese and lean mice consumed more protein when allowed to self-select, each group maintained the same energy intake as observed when a single diet was fed. Because obese mice consumed more energy than lean mice, their self-selected intake of protein was 55% greater than observed in lean mice. The increased protein intake in self-selected obese mice was associated with a decreased tryptophan:large neutral amino acid ratio in their plasma. Average nitrogen retention was only slightly less in obese mice than in lean mice, but the sites of nitrogen deposition differed considerably. Obese mice retained only 35% of their nitrogen in the carcass (skeletal muscle and skeleton) while lean mice retained 58% of their nitrogen in the carcass. In summary, young obese mice allowed to self-select from two diets varying in protein and carbohydrate consumed more protein and more energy, but deposited less nitrogen in their carcasses, than lean mice. Hyperphagia in young obese mice is not directly linked to an increased demand for dietary protein.
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PMID:Protein intake regulation and nitrogen retention in young obese and lean mice. 719 28

Plasma amino acid profiles along with hemoglobin, hematocrit, albumin, protein, blood urea nitrogen and serum creatinine values for ten patients undergoing abdominal operations were studied before operation and for 16 days there-after at different intervals. Six patients in the control group were studied in a similar manner. From the observations obtained, we concluded that total amino acid valued are a more sensitive reflection of patient nutrition in both the preoperative and postoperative periods. In future, total amino acid levels may become part of the nutritional assessment of a patient undergoing an operation. The histidine levels in plasma remain low for the longest period of time, an indication of a great need for histidine. Hence, greater attention should be paid to the histidine content of a diet or solution administered parenterally, or both. In addition, branched chain amino acids, alanine, glycine, cystine, arginine, lysine, tryptophan and threonine are required in greater quantity than the other amino acids as a result of the increased catabolism and partial starvation of the patients postoperatively. In formulation hyperalimentation solutions, an increased need for these amino acids should be kept in mind.
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PMID:Changes in plasma amino acid profiles following abdominal operations. 746 77

The use of the enzyme tryptophan side-chain oxidase, isolated from Pseudomonas XA, was explored in 3 patients with refractory acute lymphocytic leukemia. Patients were given either a low-tryptophan diet or tryptophan-free hyperalimentation, prior to and during therapy. Their plasma, separated by pheresis, was continuously passed through a tryptophan depletion column containing the immobilized tryptophan side-chain oxidase. Up to 4 plasma volumes were passed through the column daily, 5 days per week for 2-3 weeks, and plasma tryptophan levels, both free and total, were measured by high-performance liquid chromatography. Pre- and postcolumn plasma samples were collected throughout the pheresis procedure. All postcolumn plasma samples had unmeasurable tryptophan levels throughout the treatment period, whereas precolumn samples were always measurable. Generally, tryptophan levels of plasma isolated from peripheral blood decreased after therapy, but rebounded by the next day. The enzyme depletion column reduces circulating plasma tryptophan levels, and its use is well tolerated by patients. However, further development of this method will require study of the effects of diet and of the duration, interval, and frequency of use of this column on therapeutic efficacy. Problems include difficulties with extended diet compliance and apparently intensive mobilization of tryptophan from body stores, which may preclude the clinical application of this enzyme depletion column.
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PMID:Depletion of patients' plasma tryptophan using tryptophan side-chain oxidase columns. 848 47


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