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

The response to cholecystokinin (CCK) as a satiety peptide in obesity or anorexia has been tested mainly in extreme models of food intake control. In the present study, the effect of CCK-8S on food intake was investigated in a nongenetic and less-stressful model of obesity due to unspecific early postnatal overfeeding in male and female rats. Reducing the normal litter size of ten to three newborn rats on day 3 of life led to an enhanced food intake resulting in an increased body weight until adulthood. Freely fed male and female, normal and obese rats were given 10 micrograms/kg CCK-8S i.p. on day 41 and 40 micrograms/kg CCK-8S on day 91 of life and food intake was measured for 24 h. Compared with treatment with saline (i.p.) 1 day before the test, the lower dose of 10 micrograms/kg CCK-8S reduced food intake for 2 h in normal, but not in obese rats. Conversely, the higher dose of 40 micrograms/kg CCK-8S reduced food intake in both normal and obese rats for 2 h, but this effect was more evident in the obese rats. Moreover, the satiating effect of CCK-8S was more pronounced and longer lasting in male than in female rats. In summary, the data suggest that the response to CCK-8S differs in normal and obese rats and depends on sex.
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PMID:Obesity induced by unspecific early postnatal overfeeding in male and female rats: hypophagic effect of CCK-8S. 887 70

It has been proposed, but never demonstrated, that glucose-responsive neurons are essential for the long-term regulation of body weight, and that mice injected with gold-thio-glucose (GTG) become obese due to destruction of glucose-responsive neurons. To assess these hypotheses, mice were injected with either saline (control) or a dose of GTG that produces obesity, and the effects on feeding of peripheral injection of saline, glucose, 2-deoxyglucose (2-DG), or cholecystokinin (CCK) were measured. In control mice, 2-DG increased, whereas glucose and CCK decreased, food intake significantly. In contrast, in GTG-treated mice, 2-DG and glucose did not have a significant effect on food intake. The GTG-treated mice remained sensitive to the inhibitory effect of CCK on food intake. These data indicate that i.p. injection of GTG, which produces obesity, also destroys glucose-responsive neurons, consistent with the hypothesis that glucose-responsive neurons contribute to the long-term regulation of body weight.
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PMID:Injection with gold thioglucose impairs sensitivity to glucose: evidence that glucose-responsive neurons are important for long-term regulation of body weight. 889 43

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

Obesity is a major risk factor for morbidity and mortality, and a series of pharmacologic approaches are available for helping to manage the problem. Obesity is caused by an imbalance between caloric intake and energy expenditure, which is influenced by both environmental and genetic factors. Pharmacologic treatments include anorexigenic agents, which fall into two broad categories: those that act via brain catecholamine pathways and those that act via serotonin pathways. The most recent oral agents approved are dexfenfluramine, which is currently being marketed, and sibutramine. Both agents inhibit the control reuptake of serotonin but in addition may have effects on thermogenesis. Under investigation are agents that increase energy expenditure: the beta 3-adrenergic receptor agonists and drugs that prevent the intestinal absorption of free fatty acids and cholesterol. In development are innovative approaches to influence leptin and its receptors, various obesity genes, and biologic substances thought to influence satiety (neuropeptide Y, enterostatin, cholecystokinin, bombesin, and amylin). Obesity has now become a major target for drug development not only for affecting obesity per se but also for managing and preventing comorbid conditions such as diabetes and cardiovascular disease.
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PMID:The pharmacologic approach to the treatment of obesity. 920 52

The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.
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PMID:Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns. 920 88

Gallbladder disorders have been recognized with increasing frequency in pediatric patients. This study aimed to identify recent trends in management and compare the effectiveness of laparoscopic (LC) over open cholecystectomy (OC) by a retrospective chart analysis of all cholecystectomies from 1990 through 1995. Information obtained included demographics, symptoms, predisposing conditions, associated illnesses, family history, imaging studies, type of cholecystectomy, complications, operative time, pain medication, diet recommencement, pathologic findings, and length of hospital stay. The type of cholecystectomy (OC vs. LC) was compared with the clinical variables using standard statistics. Eighty-three patients between 21 months and 18 years of age were identified; their mean age was 14.8 years. Females (76%) with classic biliary symptoms predominated;12% of the patients developed gallstone pancreatitis and 7% jaundice. Abnormal liver chemistry values, obesity, and elevated triglyceride levels comprised the most significant predisposing factors. Indications for surgery were cholelithiasis in 71 patients (86%), gallbladder dyskinesia in 10 (12%), and sludge/polyp in 2. Fifty-nine cholecystectomies (71%) were done laparoscopically and 24 (29%) open. Choledocholithiasis in 6 children (7%) was managed by open extraction with t-tube placement or endoscopic papillotomy followed by LC. No major ductal complication was identified. The predominant pathologic finding was chronic cholecystitis, including the subgroup with biliary dyskinesia. Statistical comparison showed that LC is superior to OC in regard to length of stay, diet resumption, use of pain medication, operating time, and cosmetic results. It is concluded that a contemporary diet, obesity, and abnormal liver chemistry are the main predisposing conditions of gallbladder disease in children in this decade. Females in their teenage years with typical symptoms continue to be the most commonly affected group. Persistent biliary symptoms associated with low gallbladder ejection fractions during hepatobiliary cholecystokinin-stimulated scans can be caused by dyskinesia. The method of choice to remove the diseased gallbladder in children is LC, which is safe, efficient, and superior to the conventional method. Common duct stones can be managed by simultaneous endoscopic papillotomy. The costs of LC are reduced by employing reusable equipment and selective cholangiographic indications.
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PMID:Trends in management of gallbladder disorders in children. 924 96

Despite the increase in body fat and obesity that occurs with aging, there is a linear decrease in food intake over the life span. This conundrum is explained by decreased physical activity and altered metabolism with aging. Thus, older persons fail to adequately regulate food intake and develop a physiologic anorexia of aging. This physiologic anorexia depends not only on decreased hedonic qualities of feeding with aging (an area that remains controversial) but also on altered hormonal and neurotransmitter regulation of food intake. Findings in older animals and humans have provided clues to the causes of the anorexia of aging. An increase in circulating concentrations of the satiating hormone, cholecystokinin, occurs with aging in humans. In addition, animal studies suggest a decrease in the opioid (dynorphin) feeding drive and possibly in neuropeptide Y and nitric oxide. The physiologic anorexia of aging puts older persons at high risk for developing protein-energy malnutrition when they develop either psychologic or physical disease processes. Despite its high prevalence, however, protein-energy malnutrition in older persons is rarely recognized and even more rarely treated appropriately. Screening tools for the early detection of protein-energy malnutrition in older persons have been developed. Multiple treatable causes of pathologic anorexia have been identified. There is increasing awareness of the importance of depression as a cause of severe weight loss in older persons. Approaches to the management of anorexia and weight loss in older persons are reviewed. Although many drugs exist that can enhance appetite, none of these are ideal for use in older persons currently.
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PMID:Anorexia of aging: physiologic and pathologic. 973 60

Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp7 in conjunction with N-methylation of Phe8 produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.
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PMID:Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents. 943 99

Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, hyperglycemia, and non-insulin-dependent diabetes mellitus and do not express cholecystokinin A (CCK-A) receptors, the receptor subtype mediating the satiety actions of CCK. In short-term feeding tests, male OLETF rats were completely resistant to exogenous CCK, and their response to bombesin was attenuated. Comparisons of liquid meal consumption in OLETF and control Long-Evans Tokushima (LETO) rats demonstrated that 1) OLETF rats had greater intakes during 30-min scheduled daytime meals and significantly larger and fewer spontaneous night-time meals and 2) although the initial rates of licking were the same, OLETF rats maintained the initial rate longer and the rate at which their licking declined was slower. In 24-h solid food access tests, OLETF rats consumed significantly more pellets than LETO controls, and this increase was attributable to significant increases in meal size. Together, these data are consistent with the interpretation that the lack of CCK-A receptors in OLETF rats results in a satiety deficit leading to increases in meal size, overall hyperphagia, and obesity.
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PMID:Disordered food intake and obesity in rats lacking cholecystokinin A receptors. 953 Feb 26

Several clinical disorders are strongly influenced by hormones involved in appetite and weight regulation. Obesity and eating disorders are of major importance, because they are associated with severe morbidity and considered to be among the greatest health problems in the Western world today. This review describes recent findings in hormonal regulation of food intake by substances acting both centrally, such as corticotropin-releasing factor, neuropeptide Y and leptin, and peripherally, such as cholecystokinin and somatostatin. Sex hormones and glucocorticoids play an important role in long-term regulation of metabolism. The role of these hormones in appetite and weight changes during life as well as during pregnancy and lactation is discussed. Furthermore, the development of obesity and eating disorders is influenced, in particular, by steroid hormones. Treatment with sex hormones, as in hormone replacement therapy, affects appetite and weight and may have beneficial effects in preventing android obesity. Currently, there is great effort in developing endogenous neurohumoral substances into effective drugs for the treatment of obesity and eating disorders. Leptin and neuropeptide Y analogues are of interest as potential antiobesity agents.
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PMID:Hormonal regulation of appetite and food intake. 955 85


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