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

We have determined the chromosomal locations of the two cholecystokinin (CCK) receptor genes in the mouse. Genetic localization utilized an interspecific backcross panel formed from the cross (C57BL/6J x Mus spretus) F1 x Mus spretus. Genomic DNAs from 94 individuals in the backcross were analyzed by Southern hybridization with rat CCKA and CCKB receptor cDNA probes. Unique map positions were determined by haplotype analysis with 650 previously mapped loci in the mouse backcross. The CCKA receptor gene (Cckar) mapped to mouse Chromosome (Chr) 5, in tight linkage with the DNA marker D5Bir8. The CCKB receptor gene (Cckbr) mapped to mouse Chr 7, tightly linked to the beta-hemoglobin locus (Hbb). This localization places Cckbr in the same region as the mouse obesity mutation tubby (tub), which also maps near Hbb (2.4 +/- 1.4 cM). Since CCK can function as a satiety factor when administered to rodents, localization of Cckbr near the tub mutation identifies this receptor as a possible candidate gene for this obesity mutation.
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PMID:Localization of the murine cholecystokinin A and B receptor genes. 761 26

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

Cholecystokinin (CCK) and gastrin are members of an important family of gastroenteropancreatic polypeptides. Distribution of CCK both in the digestive system and central and peripheral nervous structures correlates with the variety of its actions; more than a classic hormone, CCK is a peptidergic neurotransmitter. CCK plays a predominant role in multiple digestive functions: contraction and emptying of the gallbladder, stimulation of pancreatic secretion of enzymes, delay of gastric emptying, diminution of gastric acid secretion, regulation of insulin secretion, reduction of food intake, etc. Distinction between pharmacologic and physiologic effects has been difficult in all of these areas. Modern technological procedures have generated significant progresses: reliable plasmatic bioassay, understanding of molecular heterogeneity, identification and characterization of receptors and their subtypes, agonists and antagonists, some of them currently available for research studies. The integrationist perspective of normal and pathological physiology has been considerably enhanced. Therapeutic use of CCK and its derivatives in some specific problems, i.e. obesity and anorexia, remains incipient and restricted.
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PMID:[Advances in gastrointestinal hormones: cholecystokinin]. 800 26

The neural regulation of food intake seems to be quite similar in birds and mammals. The ventromedial hypothalamic syndrome produced by lesions within the mediobasal hypothalamus of both birds and mammals is composed of several independent physiological and behavioral changes. Other neural sites known to be important in mammals for regulating food intake need to be examined in birds including the paraventricular nucleus, nucleus tractus solitarius and parabrachial nucleus. Members of the opioid and pancreatic polypeptide families are effective in stimulating food intake in avian species. Both prolactin and growth hormone are also efficacious in stimulating food intake. In contrast, cholecystokinin inhibits food intake when administered intracerebroventricularly. The autonomic and endocrine hypothesis developed to explain obesity in mammals appears to be quite applicable to genetic strains of commercial birds selected for meat production. Specifically the commercial broiler appears to display an imbalance of the autonomic nervous system. The parasympathetic nervous system dominates as a consequence of intense genetic selection for growth rate.
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PMID:Central neuroanatomical systems involved in the regulation of food intake in birds and mammals. 806 84

In addition to various psychosocial and metabolic factors, food intake is also influenced by gastrointestinal mechanisms that trigger both the initiation and termination of eating behaviors. Although gastric distension is one of the most obvious signs of "fullness" and clearly plays a role in controlling food intake, its effects are only temporary and are distinct from the feelings of satiety generally associated with a meal. Such postprandial sensations appear to be related to the activation of intestinal chemoreceptors. Other evidence indicates that the release of cholecystokinin and perhaps other transmitters as well may contribute to satiety. Although the stomach probably does not expand or shrink in response to different levels of food intake, nutrient receptors in the small intestine probably do adapt to changes in food intake. Intestinal adaptation also occurs in response to thyroid hormone, insulin, and cortisol as well as to obesity, pregnancy, and illness, which all may have an important bearing on changes in eating behavior in these situations.
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PMID:The role of the gut in regulating food intake in man. 813 94

Disturbed satiety mechanisms may contribute to obesity. There has been speculation that cholecystokinin (CCK) and pancreatic polypeptide (PP) are involved in the regulation of satiety. We have therefore investigated whether there are differences between healthy lean and healthy non-diabetic obese volunteers in plasma CCK or PP release after a neuropeptidergic stimulation with bombesin and after infusion of a mixed meal. There were no differences in plasma CCK between groups either basally or in response to either form of stimulation. However, the plasma PP concentrations after the meal were significantly less in obese (2845 +/- 404 pM.min) than in lean subjects (5569 +/- 997 pM.min), whereas the plasma PP concentrations during bombesin were similar in both groups. We tested two other groups of nine obese and lean subjects to determine whether a disturbed vagal function could be the cause of the diminished plasma PP in obese persons, by studying the effect of modified sham feeding (MSF) on plasma PP. However, there were no significant differences in the plasma PP response to MSF between lean and obese subjects. We conclude that there are no differences between lean and obese persons in plasma CCK secretion in response to infusion of the neuropeptide bombesin or to ingestion of a mixed meal. However, the plasma PP after a mixed meal, is markedly diminished in obese subjects. This could not be attributed to a disturbed vagal cephalic stimulation.
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PMID:Plasma cholecystokinin and pancreatic polypeptide secretion in response to bombesin, meal ingestion and modified sham feeding in lean and obese persons. 814 26

Peripheral signals from stomach and small intestine are believed to induce satiation. In experimental animals, satiation factors can be transfused pointing to the humoral nature of the signal. Cholecystokinin (CCK) may be an important mediator, since infusion of exogenous CCK has been demonstrated to induce satiation and to inhibit gastric emptying. However, whether this effect of CCK is a physiological or pharmacological event is a matter of controversy. The significance of exogenous CCK or stimulation of endogenous CCK in the possible treatment of obesity requires further study.
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PMID:Cholecystokinin and satiation. 831 28

In this study we examined the ability of intraperitoneal cholecystokinin COOH-terminal octapeptide (CCK-8; 0.2, 0.6, and 2.0 micrograms/kg) to suppress food intake in rats that had consumed a control diet, 6-8 g.kg-1.day-1 of ethanol (EtOH) in sucrose, or sucrose alone for 6 mo. Both the EtOH- and sucrose-fed rats developed significant dietary obesity. After 3 mo, the EtOH group was significantly more sensitive to CCK-8 than the sucrose and control groups, while the responses of the sucrose and control groups were comparable. In contrast, after 6 mo the EtOH and sucrose groups' response to CCK-8 was no longer significantly different. After 6 mo there were no significant differences in basal or postprandial plasma CCK-8 levels. The sucrose group had significantly higher basal insulin levels than the control and EtOH groups, and postprandial insulin levels, relative to basal, were significantly elevated in the EtOH group. Basal glucose levels did not differ among groups. Postprandial glucose levels (relative to baseline) were significantly lower in the EtOH group compared with the other groups and in fact never rose above baseline levels. These results are consistent with the hypothesis that EtOH, when taken on a chronic basis, increases the sensitivity to CCK-8.
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PMID:Chronic alcohol consumption increases sensitivity to the anorexic effect of cholecystokinin. 834 89

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

We have attempted to provide a progress report on current research on the role of catecholamines and serotonin receptor subtypes in feeding control. Recent evidence suggests that only some of the several catecholamine receptor subtypes are specifically involved in feeding control. They include the beta 1/2-adrenoceptors, the alpha 1-adrenoceptors and the D1 dopamine receptors: stimulation of these receptors reduces feeding in rats. Stimulation of serotonergic 5-HT1B and 5-HT2C receptors reduces feeding and perhaps enhances the satiating effect of food. Recently, an interesting reciprocal relation between serotonin and cholecystokinin has been discovered in relation to feeding control. The serotonergic 5-HT2A receptors are involved in stress-induced anorexia and regulate the hyperphagia induced by neuropeptide Y in the nucleus paraventricularis of the hypothalamus. Both effects may involve changes in the secretion of corticotropin-releasing factor. These findings may help elaborate neuronal models of feeding control and perhaps facilitate progress in the pharmacotherapy of human obesity and eating disorders.
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PMID:Pharmacology of ingestive behaviour. 876 44


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