Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma concentrations of regulatory peptides were monitored in groups of obese and normal-weight subjects following modified sham feeding and a liquid fatty meal. Following modified sham feeding a significant increase in immunoreactive cholecystokinin (CCK) in plasma was recorded in both groups. In the obese subjects, however, the concentrations following sham feeding were significantly lower than in normal-weight subjects, and the initial part of the response was negative. Basal and modified sham feeding stimulated immunoreactive pancreatic polypeptide (PP) concentrations in plasma did not differ between the groups. After the liquid fatty meal plasma CCK concentrations increased similarly in both groups. In contrast immunoreactive neurotensin and somatostatin concentrations following the meal were lower in the obese group, and a changed concentration-time pattern for somatostatin was observed in the obese group. Postprandial concentrations of PP and immunoreactive gastrin were not different in the groups. The results indicate that the plasma concentration patterns of CCK, somatostatin and NT are disarranged in obesity. The changes may promote rapid propulsion and absorption of ingested food, and facilitate deposition of fat in adipose tissue in obesity and thus may be of pathophysiological importance.
 ...
PMID:Plasma concentrations of regulatory peptides in obesity following modified sham feeding (MSF) and a liquid test meal. 134 61

Neuropeptide Y (NPY) is a powerful appetite stimulant, and hypothalamic concentrations rise after food deprivation and in experimental diabetes. Serotonergic drugs such as dexfenfluramine are inhibitors of feeding. We measured hyothalamic NPY and NPY mRNA, along with galanin, neurotensin, and somatostatin in chow-fed rats and in rats with dietary obesity, and examined the effect of dexfenfluramine on these peptides in this model. Sixty-five rats were fed a palatable diet (condensed milk, sucrose and chow) for 6 weeks, which produced significant weight gain compared to twenty fed standard chow (145.1 +/- 2.3 g vs. 113.4 +/- 3.2 g, p less than 0.001). Groups of animals were treated for 7 days or 28 days with dexfenfluramine (1.8 mg/kg/day) or saline intraperitoneally via miniosmotic pumps. Hypothalami were dissected into medial and lateral blocks, and NPY, galanin, neurotensin, and somatostatin were measured by radioimmunoassay. Neuropeptide Y mRNA was measured by Northern blotting. Hypothalamic NPY was significantly higher in the palatable diet group compared to chow-fed controls (medial hypothalamus: 86.6 +/- 7.6 vs. 65.7 +/- 4.0 pmol/g tissue, p less than 0.02, lateral hypothalamus 71.2 +/- 6.6 vs. 53.1 +/- 3.6 pmol/g tissue, p less than 0.05), but NPY mRNA was unchanged. Although dexfenfluramine was effective at reducing weight gain in the animals fed the palatable diet, this did not result in any changes in the hypothalamic neuropeptides measured. Neuropeptide Y may be of importance in diet-induced obesity but the weight loss produced by dexfenfluramine in such animals is not mediated by changes in hypothalamic NPY.
 ...
PMID:Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats. 138 31

Fenfluramine is an amphetamine derivative which is used as a weight-reducing agent in the treatment of obesity. It has been postulated that fenfluramine affects brain serotonin (5HT) neurons resulting in decreased food intake and altered autonomic outflow which, in turn, increases metabolism. CRF decreases food intake and, in addition, has been demonstrated to reduce body weight in genetically obese rats through selective activation of sympathetic and inhibition of parasympathetic outflows. Because 5HT is a potent CRF secretagogue, we tested the hypothesis that the weight-reducing effects of fenfluramine administration may be mediated, in part, through altered CRF secretion. Chronic fenfluramine treatment (1-24 mg/kg sc, twice daily, 4 days) resulted in a dose-dependent decrease in hypothalamic CRF concentration at 30 min after the final drug injection and was accompanied by a significant reciprocal increase in plasma corticosterone concentration. These data suggest that the decrease in hypothalamic CRF was a consequence of increased CRF secretion. These changes in hypothalamic CRF and plasma corticosterone correlated with brain fenfluramine levels. In contrast, high dose fenfluramine treatment significantly increased hippocampus, midbrain, and spinal cord CRF concentrations whereas levels in cerebral cortex, caudate putamen, thalamus, pons/medulla, and cerebellum were unaffected. There was no effect of this fenfluramine treatment protocol on regional brain TRH or neurotensin concentrations. In keeping with the well known development of tolerance to the weight-reducing effects of fenfluramine, chronic fenfluramine treatment resulted in lesser increases in corticosterone secretion than after acute treatment. Whereas weight loss observed after chronic fenfluramine treatment was associated with stimulation of hypothalamic-pituitary-adrenocortical hormone secretion, the weight-recovery phase after cessation of drug treatment was associated with decreased levels of plasma corticosterone. These data, demonstrating fenfluramine-induced alterations in brain CRF and plasma corticosterone, suggest that CRF may represent an important endogenous transmitter which mediates the weight-reducing effects of the drug.
 ...
PMID:Role for brain corticotropin-releasing factor in the weight-reducing effects of chronic fenfluramine treatment in rats. 164 65

The effects of oral diethylaminoethyl-dextran (3 g total), taken 30 min before a standard mixed test meal, on plasma glucose, total cholesterol, triglycerides, total lipids, gastrin-like immunoreactivity, bombesin-like immunoreactivity, gastric-inhibitory-polypeptide-like immunoreactivity and neurotensin-like immunoreactivity were evaluated in eight healthy volunteers following a double-blind protocol. Incremental peak plasma concentrations of total lipids and triglycerides were significantly reduced by pretreatment with diethylaminoethyl-dextran pretreatment, while peaks of plasma glucose and total cholesterol were not significantly affected. Diethylaminoethyl-dextran also inhibited postprandial gastrin-like gastric-inhibitory-polypeptide-like and neurotensin-like immunoreactivity; by contrast, bombesin-like immunoreactivity was not significantly modified. The present study indicates that diethylaminoethyl-dextran is able to regulate some postprandial metabolic and hormonal parameters in man; consequently it might be useful in the treatment of hyperlipoproteinaemia and obesity.
 ...
PMID:Short-term effects of diethylaminoethyl-dextran on postprandial gastrointestinal hormone responses in man. 169 37

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.
 ...
PMID:Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat. 172 Mar 64

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.
 ...
PMID:Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. 194 36

Hyperphagia and obesity are often associated, and the origins of the biochemical modifications leading to these syndromes might be in the hypothalamus. Indeed, food intake is regulated by numerous neuropeptides in various hypothalamic nuclei, including the paraventricular (PVN), arcuate (ARC), ventromedian (VMN) and suprachiasmatic (SCH) nuclei. Among these peptides, neuropeptide Y (NPY) is the most potent inducer of food intake whereas neurotensin (NT) decreases food intake. We measured these two peptides in microdissected hypothalamic nuclei in obese Zucker rats that ate 30% more food than their lean counterparts. Neuropeptide Y and neurotensin levels varied in opposite directions: In the hyperphagic obese Zucker rats, the NPY concentrations were significantly greater than those in the lean normophagic rats in the ARC (+30%), PVN (+60%) and SCH (+94%) nuclei, whereas the NT levels were significantly lower in the ARC (-40%), PVN (-31%) VMN (-66%) and SCH (-47%) nuclei. Both these variations tend to increase food intake. Feeding periodicity might also be modified because large variations of the two peptides have been measured in the supra-chiasmatic nucleus, which is considered the most important regulator of feeding rhythm. The results reinforce the hypothesis that hyperphagia in obesity is associated with a biochemical modification in the central nervous system because the peripheral status of NT and NPY was not modified in the obese rats. Because levels of other hypothalamic peptides, such as opioid peptides and somatostatin, are also slightly modified, it can be concluded that hyperphagia in obesity is associated with a central peptidergic dysregulation. Research on drugs reacting specifically with the receptor of these peptides might have interesting implications for the treatment of hyperphagia and, therefore, of obesity.
 ...
PMID:Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats. 236 13

Immunoreactive neurotensin was measured in plasma and acid-ethanol extracts of brain, intestine and pancreas of obese hyperglycaemic (ob/ob) mice of the Aston strain, C57BL/KsJ diabetes-obese (db/db) mice, and their respective lean controls. In lean mice, the intestine was the major source of neurotensin (156-194 mg/g wet weight and 169-361 ng/intestine), with smaller amounts in the brain (33-43 ng/g and 13-17 ng/brain), pancreas (0.8-1.1 ng/g and 0.28-0.32 ng/pancreas) and plasma (50-100 pg/ml). Compared with lean controls, ob/ob and db/db mice exhibited 13 and 23% decreases in brain weight, and 37 and 82% increases in intestinal weight. Concentrations of neurotensin in plasma and brain were similar in lean and obese-diabetic mutant mice, but the total content of brain neurotensin was 25% lower in ob/ob mice. Neurotensin was unchanged in the pancreas of db/db mice. However, raised concentrations and total contents of neurotensin were observed in the pancreas of ob/ob mice (72 and 57%, respectively) and the intestine of both ob/ob (56 and 118%) and db/db (35 and 144%) mice. These observations raise the possibility that increased neurotensin concentrations might exert local effects in the intestine and pancreas which contribute to the pathogenesis of obesity-diabetes syndromes in mice.
 ...
PMID:Immunoreactive neurotensin in spontaneous syndromes of obesity and diabetes in mice. 388 30

There is evidence for involvement of gastrointestinal hormones in pathogenesis of obesity and reports on lipolytic activity in animals. The in vitro lipolytic activity of these hormones was tested in human adipocytes. Vasoactive intestinal polypeptide, glucagon, secretin, human gastrin I, gastrin releasing polypeptide, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, bombesin, neurotensin, C-peptide, as well as cholecystokinin did not stimulate lipolysis significantly above basal. These results indicate that the involvement of these hormones in obesity in man might not be due to a direct lipolytic effect on the human adipocyte.
 ...
PMID:Glycerol release from incubated human adipocytes is not affected by gastrointestinal peptides. 401 16

The plasma concentration of neurotensin-like immunoreactivity (p-NTLI) was measured after oral intake of fat in (a) healthy non-obese volunteers, (b) grossly obese but otherwise healthy persons, and (c) patients who had undergone jejunoileal bypass because of gross obesity. In addition, p-NTLI was measured after intravenous infusion of fat in healthy non-obese volunteers. Basal p-NTLI levels were significantly higher in the patients with bypass than in the obese group. After oral intake of fat, the increase in p-NTLI was much greater and more sustained in the bypass group than in the two other groups. The type of bypass (end-to-end, end-to-side or biliointestinal) and the time after the operation did not correlate with the p-NTLI response. Intravenous infusion of fat evoked no increase in p-NTLI. To produce a rise in p-NTLI level, therefore, the fat does not have to be absorbed and hematogenously distributed to the N-cells (neurotensin-storing cells). This observation may suggest that direct contact between chyme and the N-cells, or local neural or hormonal factors, are required to stimulate release of NTLI. The authors suggest that increase in the postprandial release of neurotensin may promote the diarrhoea after bypass operations, and possibly has other physiologic effects in such patients.
 ...
PMID:Neurotensin-like immunoreactivity in plasma after fat intake in normal and obese subjects and after jejunoileal bypass. 403 91


1 2 3 4 5 6 Next >>