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

The pancreatic islet hormone secretion is modulated by one or more gastrointestinal peptides ("gut-factor") secreted in response to various types of ingested nutrients. Among a number of postulated candidates for the putative "gut-factor", the gastric inhibitory polypeptide (GIP) has recently emerged as a most likely enteric signal of physiologic import, although its precise role in the pathophysiology of diabetes mellitus remains incompletely understood. During the past decade, an avalanche of knowledge has accumulated regarding a number of peptide agents common to the gastro-enteric-pancreatic system and the nervous system. Preliminary evidence indicates a potential role of several of these peptides in the pathophysiology of diabetes. For instance, cholecystokinin and human pancreatic polypeptide (hPP) may be importantly involved in the regulation of appetite and satiety control and the development of obesity whereas somatostatin, "endorphins", and neurotensin may directly or indirectly modulate islet hormone secretion. Finally the significance of the recently demonstrated presence of insulin and glucagon or glicentin-like peptides in the brain requires close scrutiny.
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PMID:The role of gastrointestinal and neuronal peptides in the pathophysiology of diabetes mellitus. 612 74

The meal stimulated neurotensin release was studied in morbidly obese patients in whom gastric partitioning was performed as treatment for the obesity. Basal neurotensin and the early postprandial response were not altered by the operation. However, the late phase response between 60 and 150 min was depressed, the integrated response being 1.27 (s.e.m. = 0.22) nmol/l. min postoperatively, to 1.66 (s.e.m. = 0.32) nmol/l. min preoperatively (P less than 0.05). As neurotensin is a peptide which inhibits gastric acid secretion and stimulates pancreatic bicarbonate release, long term ulcerogenic effects of gastric partitioning operations should be considered.
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PMID:Meal stimulated neurotensin release following gastric partitioning for morbid obesity. 657 63

Current thinking concerning the possible role off neurotensin in disease is reviewed. The type of approach used in this article is to summarize the results of studies concerning release of neurotensin-like immunoreactivity and to describe the effects of neurotensin which may be of physiological significance such as changes in gastrointestinal motility from a fasting to a fed type in gastric acid secretion and vasoconstriction in adipose tissue. The possible involvement of neurotensin in motility disturbances, duodenal ulcer and obesity has also been discussed. In addition, studies concerning the role of neurotensin in endocrine tumours are presented.
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PMID:The role of neurotensin in disease. 657 28

The concentration of cholecystokinin (the octapeptide, CCK-8), bombesin, and neurotensin was measured by radioimmunoassay in the cortex, hypothalamus and diencephalon of brains from lean, genetically obese and hypothalamic (VMH) obese rodents. Highest concentration of CCK-8 was found in the cortex whereas highest concentrations of bombesin and neurotensin were in the hypothalamus. When food was provided ad libitum, there was no difference in concentration of any of these peptides between lean and the respective genetically obese mice (ob/ob) and fatty (fa/fa) rats, or between lean and hypothalamic (VMH lesioned) obese rats. Adrenalectomy, which arrested the progression of obesity in both ob/ob and fatty rats, did not result in significant change in concentration of any of the three peptides studied in comparison with the respective sham-operated animals. Though significant differences in cholecystokinin and bombesin concentrations were detectable in some instances between adrenalectomized lean and adrenalectomized obese rats, these differences did not appear to be related to fall in food intake or slowing of body weight gain. Thus a variety of manipulations which altered the nutritional plane of the experimental rodents was not accompanied by significant changes in brain concentrations of cholecystokinin, bombesin or neurotensin.
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PMID:Cholecystokinin, bombesin and neurotensin in brain tissue from obese animals. 672 99

The treatment of obesity by intestinal bypass provides a unique model for the investigation of gut hormone release from the functionally deranged bowel. We have examined the postprandial response of eight circulating gut or pancreatic peptide hormones in 16 preoperative obese patients, 20 patients with jejunoileal bypass, 38 patients with biliopancreatic bypass and 13 age and sex-matched controls. Basal and post-meal hormone concentrations were determined by specific radioimmunoassay methods. Reductions of the upper small intestinal hormones, motilin and gastric inhibitory polypeptide were found in both types of surgery. Conversely, the ileal hormones neurotensin and enteroglucagon were elevated following surgery. This pattern is consistent with the known distribution of these hormones. Variations of response due to surgical differences were noted for gastrin and the enteropancreatic axis, which was more markedly disturbed after biliopancreatic bypass. The alterations of hormone release closely reflect the anatomical changes induced by each particular surgical technique.
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PMID:Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity. 679 32

Biliopancreatic bypass for obesity entails a 2/3 distal gastrectomy with Roux-en-Y reconstruction, being the small bowel transected at its midpoint and the enteroenteroanastomosis place 50 cm proximal to the ileocecal valve. Neurotensin and enteroglucagon fasting and meal-stimulated plasma concentrations were determined in 13 nonobese healthy volunteers, in 13 nonoperated obese patients, in 11 subjects within two months, in 12 subjects four to twelve months and in 7 subjects fifteen to twenty months after operation. Basal plasma enteroglucagon was significantly higher in the obese group than in the controls. However, there was no difference in the peak response, and a decrease, though not statistically significant, was seen in the integrated response. All three values were strikingly augmented in the 0-2 month group, with a highly significant difference from the preoperative group. The 4-12 and 15-20 month groups, in comparison with the 0-2 month group, showed no changes in fasting levels, a clear-cut decreased peak response and a sharp progressive reduction in integrated response, mean value in the 15-20 month group being significantly lower than that of 0-2 month group. Neurotensin basal and meal-stimulated peak plasma concentrations in the obese group were significantly higher than in the control group, whilst the integrated response was almost identical in the two groups. In postoperative groups no substantial changes in fasting levels and an increase in the peak response were observed, with a considerable progressive rise in the integrated response.
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PMID:[Behavior of plasma enteroglucagon and neurotensin in obese patients subjected to biliopancreatic bypass]. 745 2

Neurotensin (NT) inhibits food intake when injected either in brain ventricles or in hypothalamic nuclei such as the ventromedian nucleus (VMN). NT concentrations are lower in obese than in lean Zucker rats in several hypothalamic nuclei, including the VMN. In this experiment, we studied the influence of the feeding state on NT concentrations in different brain areas of 10-week-old lean (n = 27) and obese (n = 27) Zucker rats that were fasted for 48 hours and then refed for 6 hours. NT level was measured in the microdissected areas by radioimmunoassay. Obese rats ingested approximately 50% more food than lean rats in the ad libitum (ad lib) condition (P < .001) and 12% more during the refeeding time (NS). NT concentrations in the median eminence (ME) were 50% lower in obese than in lean rats (P < .001). This decrease could be related to a 20% decrease in the arcuate nucleus (ARC) of the obese rats (P < .04). NT concentrations in the ME and ARC, which are important for the control of pituitary hormone secretion by NT, were not changed by the feeding state in both genotypes. NT varied with the feeding state in the VMN only (P < .04). Concentrations were 45% lower in fasted (FD) obese rats than in ad lib or refed (RF) obese rats (1.09 +/- 0.25 ng/mg protein v 1.98 +/- 0.36 ad lib and 1.62 +/- 0.11 RF, P < .05). They remained unchanged in lean rats. NT variations in the VMN of obese rats could contribute synergistically with other neuropeptides to the abnormal feeding behavior of these rats.
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PMID:Neurotensin decreases with fasting in the ventromedian nucleus of obese Zucker rats. 763 54

Gastrointestinal motility is closely linked to the rate at which nutrients become systemically available. Regulation of gastric emptying represents the most important brake against delivery of nutrients to the intestine in excess of digestive and absorptive capacity. In man, gastric emptying is slowed in proportion to the energy density of the meal, which will level out the rate of energy delivery to the duodenum. Studies suggest a more rapid gastric emptying in obesity, although the opposite has been reported in some experimental settings. Moreover, gastric volume is larger in obese individuals and appropriate satiety signals are not triggered in response to gastric distension. Postprandial intestinal transit time in obesity is similar to that in normal-weight subjects, however, despite this fact, intestinal absorption of nutrients is more efficient in obesity. Several regulatory mechanisms for gastrointestinal motility, such as the autonomous and enteric nervous systems and gastrointestinal regulatory peptides, are also of importance for feeding behaviour and metabolism. Dysfunction of the autonomous nervous system has been observed, the sensitivity to cholecystokinin is decreased in obesity, and plasma concentrations of somatostatin and neurotensin are lower than in normal-weight subjects. These changes in regulatory mechanisms favour rapid gastrointestinal transit of ingested nutrients and promote rapid intestinal absorption in obesity and decreased satiety in response to ingested food. It is presently not known whether the observed changes in gastrointestinal motility in obesity represent a primary feature linked to the pathogenesis of such disease.
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PMID:Gastrointestinal motility in obesity. 771 65

Mice homozygous for the fat mutation exhibit marked hyperpro-insulinemia and develop late onset obesity. The fat mutation was recently mapped to the gene encoding carboxypeptidase E (CpE), a processing enzyme involved in trimming C-terminal paired basic residues from prohormone-derived peptides. The mutation resulted in a loss of CpE activity that correlated with aberrant proinsulin processing. Neurotensin (NT) and melanin-concentrating hormone (MCH) are two neuropeptides that, among other central effects, inhibit food intake. Here, using RIA techniques coupled to reverse phase HPLC, we analyzed the processing products derived from the NT and MCH precursors in the brain of +/fat and fat/fat mice. Compared to control hypothalamic and brain extracts, fat/fat extracts had markedly reduced levels (>80%) of NT and neuromedin N (NN), another active pro-NT-derived peptide. In contrast, they exhibited high concentrations of biologically inactive NT-KR and NN-KR (NT and NN with a C-terminal Lys-Arg extension), two peptides that were undetectable in control extracts. MCH, which is located at the C-terminus of its precursor, was present in 2- to 3-fold higher amounts in fat/fat than in +/fat hypothalamus. Neuropeptide-Glu-Ile, another pro-MCH-derived neuropeptide separated from MCH by an Arg-Arg sequence, was present in amounts similar to those of MCH in control extracts. In contrast, neuropeptide-Glu-Ile was more than 10 times less abundant than MCH in extracts from obese mice. Our data are consistent with a deficit in CpE activity affecting the maturation of both pro-NT and pro-MCH. This suggests that abnormal neuropeptide and hormone precursor processing is a general phenomenon in fat/fat mice and supports the idea that defects in the production of neuropeptide involved in the control of feeding might lead to the development of obesity in these animals.
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PMID:Impaired processing of brain proneurotensin and promelanin-concentrating hormone in obese fat/fat mice. 877 Sep 19

Obesity is common and its prevalence is rising. In Singapore, a national health survey in 1992 showed that 5% of the adult population were obese and 21% were overweight. Obesity causes much morbidity and mortality and treatment is desirable. The majority of obese patients have no known cause but it is essential to exclude any underlying cause before treatment. Antiobesity drugs should be used as an adjunct to an adequate programme of dietary restriction, exercise and behavior modification. Serotonergic drugs and adrenergic agents are available in the treatment of obesity. The short-term efficacy and safety of antiobesity drugs such as fenfluramine and d-fenfluramine are proven. The long-term use of antiobesity drugs used singly or in combination remains to be established. Many peptides (cholecystokinin, glucagon, bombesin, neurotensin, etc) with weight reduction properties are undergoing extensive studies: their clinical applications are experimental. The treatment of obesity is difficult and frustrating and antiobesity drugs have an established short-term role. In morbid obesity where the life of the patient is in danger, surgery such as gastric plication may be life-saving. The recent discovery of leptin (1994) and neuropeptide Y (1995) are important breakthrough in obesity research; hopefully further research may produce more effective treatment of obesity in man.
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PMID:Current management of obesity. 894 35


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