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

Obesity occurs in 60% of women after menopause and is characterized by an excess of adipose tissue that depends on several orexigenic (neuropeptide Y (NPY) stimulates carbohydrate ingestion, galanin stimulates fat intake) and anorectic (leptin, cholecystokinin (CCK)) factors. Both leptin and insulin can reduce hypothalamic NPY production and secretion. Behavior related to the consumption of food is probably attributed to the NPY-galanin signalling route. We investigated basal levels of serum leptin, CCK, galanin and NPY in 16 non-obese premenopausal women, in 15 obese premenopausal women (body mass index (BMI) 34.6 +/- 1.3 SD) and in ten obese postmenopausal women (BMI 34.7 +/- 1.5 SD) to determine the relationship between obesity, menopause and these neuropeptides. Obese premenopausal women had three-fold elevations of serum leptin (32.1 +/- 3.2 ng/ml) in comparison to non-obese premenopausal women (10.3 +/- 1.5 ng/ml), but similar levels to those in obese postmenopausal women (35.3 +/- 4.1 ng/ml). In all 44 patients and in both sub-groups of premenopausal and postmenopausal women, serum leptin exhibited a strong positive correlation with BMI (r = 0.8692, p < 0.0001; r = 0.8803, p = 0.0001; r = 0.8184, p = 0.0001, respectively). Serum galanin values showed a statistically significant increment in the obese postmenopausal group (51.1 +/- 8.1 pg/ml) compared to both premenopausal groups: the non-obese (34.9 +/- 5.8 pg/ml) and the obese (36.0 +/- 5.5 pg/ml). Non-obese menstruating women demonstrated NPY levels (175.0 +/- 12.8 pg/ml) significantly higher than those of obese premenopausal women (126.0 +/- 12.1 pg/ml) and obese postmenopausal women (138.1 +/- 15.4 pg/ml). CCK values showed no differences between non-obese and obese pre- and postmenopausal groups. Basal insulin values were elevated in both obese groups compared to non-obese premenopausal women. Significantly increased leptin and galanin levels in postmenopausal obese women coupled with decreased NPY levels revealed some changes in the neuropeptides regulating eating behavior, which may be the reason for the onset of postmenopausal obesity.
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PMID:Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels. 1092 81

The pathophysiology of obesity is complex with many different pathways involved. A better understanding of these weight-regulating mechanisms has lead to the identification of new targets for anti-obesity agents. Most attention has been given to the centrally acting neuropeptides regulating food intake. Leptin, playing a key-role, exerts its action through several neuropeptides such as neuropeptide Y, alpha-melanocyte stimulating hormone and agouti related protein. Cocaine- and amphetamine-regulated transcript peptide and the orexins are the latest discovered peptides acting at the level of the hypothalamus. Targets for new drugs acting on peptides secreted from the periphery are cholecystokinin and glucagon-like peptide 1. Another potential target in the treatment of obesity is increasing energy expenditure via beta3 adrenoceptors or uncoupling proteins. These new pharmacological agents in development could be valuable adjuncts to more traditional treatment strategies such as dietary treatment, behavioural/psychological counselling and physical activity.
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PMID:Promising new approaches to the management of obesity. 1092 26

The neuropeptides, monoamines and many drugs involved with modulating food intake and fat stores have reciprocal effects on sympathetic activity and thermogenesis. Both serotonin, acting through 5HT1B/2C receptors, and norepinephrine acting through beta2 and/or beta3 receptors reduce food intake and augment sympathetic activity. Neuropeptide Y, beta-endorphin, orexin, galanin and melanin concentrating hormone all increase food intake and, where tested, reduce sympathetic activity. In contrast, a larger number of peptides including cholecystokinin, corticotrophin-releasing hormone/urocortin, enterostatin, leptin, CART and alpha-MSH reduce food intake and increase sympathetic activity. Nicotine, prostaglandin, dexfenfluramine and sibutramine also have this reciprocal effect on feeding and sympathetic nervous system (SNS) activity. Chronic administration of neuropeptide Y (NPY) can produce chronically increased food intake and obesity. This syndrome is similar to the ventromedial hypothalamus (VMH) syndrome and suggests that NPY must be acting as an inhibitory signal to stimulate a feeding system and inhibit sympathetic activity. The melanocortin receptor system may be particularly important in modulating food intake, because a transgenic mouse which does not express melanocortin-4 receptors is massively overweight. Adrenal glucocorticoids are important in obesity since adrenalectomy will reverse or prevent the development of all forms of obesity. The clinical importance of the sympathetic nervous system and food intake is emphasized by the inverse relation of sympathetic activity and body fat. The inhibition of food intake, lower body fat stores and higher energy expenditure in smokers also support this hypothesis. The reciprocal relationship between food intake and sympathetic activity is robust, suggesting that beta receptors in the periphery and brain may be involved in the control of feeding and a reduction in food intake in humans accounts for most of the weight loss with ephedrine and caffeine. We conclude that the inhibition of feeding by activating the SNS is an important satiety system which helps regulate body fat stores.
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PMID:Reciprocal relation of food intake and sympathetic activity: experimental observations and clinical implications. 1099

Obesity is an important factor predisposing to type 2 diabetes mellitus, especially for postmenopausal women. Experimental studies provided evidences that leptin, cholecystokinin (CCK), galanin (GAL), neuropeptide Y (NPY) and insulin are involved in feeding behaviour. The aim of the study was to evaluate their possible relationships in obese and diabetic women. Three groups of postmenopausal women (FSH > 30 mIU/ml) were evaluated: 8 diabetic (mean age 56.6 +/- 6.9 y, BMI 29.8 +/- 5.3 kg/m2), 10 obese non-diabetic (mean age 49.6 +/- 5.4 y, BMI 36.0 +/- 3.7 kg/m2) and 12 non-diabetic controls (mean age 52.7 +/- 3.5 y, BMI 27.3 1.9 kg/m2). For each patient BMI and WHR were measured and calculated. Blood samples were collected at 8:00 a.m. after an overnight fast. Plasma concentrations of FSH, leptin, CCK, GAL, NPY and insulin were determined using commercial RIA kits. Mean plasma NPY concentration was significantly higher in diabetic women than in controls (190.1 pg/ml +/- 85.4 vs 120.4 +/- 36.6). Compared to controls, mean plasma leptin level was significantly higher in obese non-diabetic women (32.9ng/ml +/- 9.2 vs 18.9 +/- 9.1). No significant differences were found between obese non-diabetic and diabetic women. In diabetic subjects positive correlations were found between: CCK and leptin (r= 0.8295; P= 0.011), CCK and insulin (r=0.7832; P=0.022), leptin and insulin (r=0.9302; P=0.001). In obese subjects a positive correlation between WHR and GAL (r= 0.6624; P= 0.037) and a negative between GAL and insulin (r= -0.6795; P= 0.031) were found. In controls positive correlations were found between WHR and CCK (r=0.6412; P=0.025), GAL and insulin (r=0.630; P=0.028) and negative between CCK and NPY (r = -0.6505; P= 0.022). Our results, ie higher mean plasma NPY levels in postmenopausal diabetic women and positive correlation of CCK with leptin and insulin, may suggest the role of these neuropeptides in metabolic disorders leading to type 2 diabetes mellitus.
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PMID:Plasma insulin, cholecystokinin, galanin, neuropeptide Y and leptin levels in obese women with and without type 2 diabetes mellitus. 1099 41

Food intake is a regulated system. Afferent signals provide information to the central nervous system, which is the centre for the control of satiety or food seeking. Such signals can begin even before food is ingested through visual, auditory and olfactory stimuli. One of the recent interesting findings is the demonstration that there are selective fatty acid taste receptors on the tongue of rodents. The suppression of food intake by essential fatty acids infused into the stomach and the suppression of electrical signals in taste buds reflect activation of a K rectifier channel (K 1.5). In animals that become fat eating a high-fat diet the suppression of this current by linoleic acid is less than that in animals that are resistant to obesity induced by dietary fat. Inhibition of fatty acid oxidation with either mercaptoacetate (which blocks acetyl-CoA dehydrogenase) or methylpalmoxirate will increase food intake. When animals have a choice of food, mercaptoacetate stimulates the intake of protein and carbohydrate, but not fat. Afferent gut signals also signal satiety. The first of these gut signals to be identified was cholecystokinin (CCK). When CCK acts on CCK-A receptors in the gastrointestinal tract, food intake is suppressed. These signals are transmitted by the vagus nerve to the nucleus tractus solitarius and thence to higher centres including the lateral parabrachial nucleus, amygdala, and other sites. Rats that lack the CCK-A receptor become obese, but transgenic mice lacking CCK-A receptors do not become obese. CCK inhibits food intake in human subjects. Enterostatin, the pentapeptide produced when pancreatic colipase is cleaved in the gut, has been shown to reduce food intake. This peptide differs in its action from CCK by selectively reducing fat intake. Enterostatin reduces hunger ratings in human subjects. Bombesin and its human analogue, gastrin inhibitory peptide (also gastrin-insulin peptide), reduce food intake in obese and lean subjects. Animals lacking bombesin-3 receptor become obese, suggesting that this peptide may also be important. Circulating glucose concentrations show a dip before the onset of most meals in human subjects and rodents. When the glucose dip is prevented, the next meal is delayed. The dip in glucose is preceded by a rise in insulin, and stimulating insulin release will decrease circulating glucose and lead to food intake. Pyruvate and lactate inhibit food intake differently in animals that become obese compared with lean animals. Leptin released from fat cells is an important peripheral signal from fat stores which modulates food intake. Leptin deficiency or leptin receptor defects produce massive obesity. This peptide signals a variety of central mechanisms by acting on receptors in the arcuate nucleus and hypothalamus. Pancreatic hormones including glucagon, amylin and pancreatic polypeptide reduce food intake. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte-stimulating hormone, growth hormone and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides that modulate feeding. beta-Casomorphin, a heptapeptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group, including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines and thyrotropin-releasing hormone, all decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors that relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
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PMID:Afferent signals regulating food intake. 1099 53

This review focuses on the expression, content, and release of neuropeptides and on their role in the development of obesity in animal models with single-gene mutations. The balance between neuropeptides that contribute to the control of feeding behavior is profoundly and variously altered in these models, supporting the concept of the existence of several types of obesity. The hypothalamic neuropeptide Y (NPY) and the pro-opiomelanocortin (POMC) systems are the networks most studied in relation to energy intake. Both receive information about the nutritional status and the level of energy storage through insulin and leptin signaling mediated by specific receptors located on POMC and NPY neurons present predominantly in the arcuate nucleus (ARC). When leptin signaling is defective, through a defect in either the receptor (Zucker fa/fa rat, cp/cp rat, and db/db mouse) or in the peptide itself (ob/ob mouse), the NPY system is upregulated as shown by mRNA overexpression and increased peptide release, whereas the content and/or release of some inhibitory peptides (neurotensin, cholecystokinin) are diminished. For the POMC system, there is a complex interaction between the tonic inhibition of food intake exerted by alpha-melanocyte-stimulating hormone (alpha-MSH) and the Agouti-related protein at the level of the type 4 melanocortin receptor. The latter peptide is coexpressed with NPY in the ARC. Corticotropin-releasing factor (CRF) is the link between food intake and environmental factors. It not only inhibits food intake and prevents weight gain, likely through hypothalamic effects, but also activates the hypothalamo-pituitary axis and therefore contributes to energy storage in adipose tissue. The factors that prod the CRF system toward the hypothalamic or hypothalamo-pituitary axis system remain to be more clearly defined (comodulators, connections between limbic system and ARC, cellular location, and type of receptors, etc. ). The pathways used by all of these neuromodulators include numerous brain areas, but some interest has returned to the classic ones such as the ventromedial and lateral hypothalamic areas because of the recent discovery of some peptides (orexins and melanin-concentrating hormone for the lateral hypothalamus) and receptors (CRF type 2 in the ventromedial hypothalamus). All of these pathways are redundant and function in a coordinated manner and sometimes by the novel expression of a peptide in an unusual area. The importance of such a phenomenon in obesity remains to be determined. Even if single-gene mutations are exceptions in human obesity, the study of genetic animal models of obesity has greatly contributed to the understanding of the regulation of feeding behavior and will allow researchers to develop new drug treatments for obesity that have to be associated with drastic changes in lifestyle (feeding, work habits, and physical activity) for a complete efficiency.
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PMID:Neuropeptides and obesity. 1105 97

Ammonium perfluorooctanoate is a potent synthetic surfactant used in industrial applications. It rapidly dissociates in biologic media to perfluorooctanoate [CF3(CF2)6CO2-], which is the anion of perfluorooctanoic acid [PFOA, CF3(CF2)6COOH]. PFOA is a peroxisome proliferator known to increase the incidence of hepatic, pancreas and Leydig cell adenomas in rats. The pancreas acinar cell adenomas may be the consequence of a mild but sustained increase of cholecystokinin as a result of hepatic cholestasis. Although no significant clinical hepatic toxicity was observed, PFOA was reported to have modulated hepatic responses to obesity and alcohol consumption among production workers. To further assess these hypotheses, we examined medical surveillance data of male workers involved in ammonium perfluorooctanoate production in 1993 (n=111), 1995 (n=80) and 1997 (n=74). Serum PFOA was measured by high-performance liquid chromatography mass spectrometry methods. Plasma cholecystokinin was measured (only in 1997) by the use of direct radioimmunoassay. Serum biochemical tests included hepatic enzymes, cholesterol and lipoproteins. Serum PFOA levels, by year, were: 1993 (mean 5.0 ppm, SD 12.2, median 1.1 ppm, range 0.0-80.0 ppm); 1995 (mean 6.8 ppm, SD 16.0, median 1.2 ppm, range 0.0-114.1 ppm); and 1997 (mean 6.4 ppm, SD 14.3, median 1.3 ppm, range 0.1-81.3 ppm). Cholecystokinin values (mean 28.5 pg/ml, SD 17.1, median 22.7 pg/ml, range 8.8-86.7 pg/ml) approximated the assay's reference range (up to 80 pg/ml) for a 12 hour fast and were negatively, not positively, associated with employees' serum PFOA levels. Our findings continue to suggest there is no significant clinical hepatic toxicity associated with PFOA levels as measured in this workforce. Unlike a previously reported observation, PFOA did not appear to modulate hepatic responses to either obesity or alcohol consumption. Limitations of these findings include: 1) the cross-sectional design as only 17 subjects were common for the three surveillance years; 2) the voluntary participation that ranged between 50 and 70 percent; and 3) the few subjects with serum levels > or = 10 ppm.
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PMID:Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. 1107 97

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.
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PMID:Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects. 1107 97

In developmental terms, the endocrine system of neither the gut nor the pancreatic islets has been characterized fully. Little is known about the involvement of cholecystokinin (CCK), a gut hormone, involved in regulating the secretion of pancreatic hormones, and pancreatic growth. Here, we tracked CCK-expressing cells in the intestines and pancreata of normal mice (BALB/c), Non Obese Diabetic (NOD) mice and interferon (IFN)-gamma transgenic mice, which exhibit pancreatic regeneration, during embryonic development, the postnatal period and adulthood. We also questioned whether IFN-gamma influences the expression of CCK. The results from embryonic day 16 showed that all three strains had CCK in the acinar region of pancreata, and specifically in alpha cells that also expressed glucagon. However, in adulthood only BALB/c and NOD mice continued this pattern. By contrast, in IFN-gamma transgenic mice, CCK expression was suppressed from birth to 3 months of age in the pancreata but not intestines. However, by 5 months of age, CCK expression appeared in the regenerating pancreatic ductal region of IFN-gamma transgenic mice. In the intestine, CCK expression persisted from fetus to adulthood and was not influenced by IFN-gamma. Intestinal cells expressing CCK did not co-express glucagon, suggesting that these cells are phenotypically distinct from CCK-expressing cells in the pancreatic islets, and the effect of IFN-gamma on CCK varies depending upon the cytokine's specific microenvironment.
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PMID:Cholecystokinin expression in the developing and regenerating pancreas and intestine. 1131 40

An Otsuka Long-Evans Tokushima Fatty (OLETF) strain of rat spontaneously developed hyperglycemia, hyperinsulinemia, insulin resistance and mild obesity, which had been studied as animal model for type II diabetes mellitus (T2DM). Recently, we observed that this strain coincidentally developed atypical hyperplasia of the choledocho-pancreatic ductal epithelium with a complete incidence. In an effort to locate genes responsible for this hyperplasia, we prepared 288 backcross progeny from a mating between OLETF rats and BN rats (which do not develop hyperplasia), and performed a genome-wide scan using 207 polymorphic genetic markers. We observed a prominent association of hyperplasia with a region involving a marker locus D14Mit4 (P = 0.00020, Fisher's exact test) and Cckar (the cholecystokinin-A receptor gene; P = 0.00025, Fisher's exact test) which is known to be disrupted in an OLETF strain. Our findings indicated that epithelial hyperplasia of the choledocho-pancreatic duct is associated with a region on rat chromosome 14 around the Cckar gene in an additive fashion with another two susceptible loci, each on chromosome 9 and 7. This implied the possibility that Cckar deficiency could result in a predisposition towards pancreatic duct hyperplasia.
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PMID:Genetic analysis of pancreatic duct hyperplasia in Otsuka Long-Evans Tokushima Fatty rats: possible association with a region on rat chromosome 14 that includes the disrupted cholecystokinin-A receptor gene. 1132 27


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