cholecystokinin and Obesity--Morbid

Bariatric surgery is the only effective treatment for morbid obesity in the long term. Gut hormones are key players in the metabolic mechanisms causing obesity. Furthermore gut hormones are involved in the signalling process of hunger and satiety which leads to the control of nutrient intake. In this review, the role of these hormones as facilitators of appetite control after bariatric and metabolic surgery will be explored.

Topics: Animals; Appetite Regulation; Bariatric Surgery; Cholecystokinin; Eating; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Obesity, Morbid; Peptide YY; Satiation; Satiety Response; Weight Loss

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several disease states such as diabetes, hypertension, cardiac disease and restrictive lung disease. When effective medical treatment of obesity becomes available, it will depend in part upon understanding the physiologic factors that control satiety. This review summarizes the information available on brain and gut control mechanisms of satiety. Brain nuclei located in the lateral hypothalamus, ventromedial hypothalamus, and other paraventricular areas are the sites of action for potent neuropeptides, such as cholecystokinin (CCK) and neuropeptide Y, that appear to regulate feeding. Exogenous CCK has been used clinically to decrease meal size in obese patients. The sites of the satiety cascade that are most often manipulated are the gastric and intestinal phases. Physiologic gastric distension is a potent inhibitor of feeding, whereas the intermeal interval may be regulated by intestinal signals released by food in the gut. Jejunal-ileal bypass has fallen from favor and has been replaced by gastric restrictive procedures that create a small proximal gastric pouch that empties into the small bowel (gastric bypass) or the distal stomach (gastroplasty). These operations rely partially on their ability to produce gastric distension in the proximal gastric pouch at an early stage during a meal. Thus, failure results if the pouch compensates by distending or if the stoma widens with subsequent loss of slow emptying. Improved medical and surgical treatment will be designed to intervene at specific sites of the satiety cascade as knowledge of the physiologic control mechanisms of satiety increases.

Topics: Bombesin; Cholecystokinin; Humans; Hypothalamus; Neuropeptide Y; Obesity, Morbid; Pancreatic Polypeptide; Satiation; Stomach

The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood.. In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)).. In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (p < 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (p < 0.012 vs. LRYGB).. Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms.

Topics: Adult; Blood Glucose; Cholecystokinin; Female; Gastric Bypass; Gastrointestinal Hormones; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Laparoscopy; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss

Jejunoileal bypass surgery for obesity increases the risk of gallstone formation, and, contrary to expectations, the incidence is greater in patients with a long as compared to a short ileum left in continuity. Impaired gallbladder motility due to reduced cholecystokinin (CCK) stimulation could be an explanation. The aim of this study was to investigate the CCK levels in such patients.. The randomized trial of bypass surgery named The Danish Obesity Project.. We compared plasma levels of CCK in obese patients at three, nine or 15 months after jejunoileal bypass surgery with either a 1:3 jejunoileal ratio (n = 14) or a 3:1 ratio (n = 15), and in unoperated obese patients (n = 7). Plasma CCK levels were determined during fasting and during 150 min following ingestion of a liquid test meal.. There were no significant changes over time following surgery. Basal CCK levels were significantly increased after surgery, and significantly higher in those with a 3:1 than in those with a 1:3 jejunoileal ratio. The postprandial AUC (mean +/- SEM) was 935 +/- 71 pM x min in the 3:1 ratio group and 891 +/- 100 pM x min in the 1:3 ratio group. This difference was not significant, but both bypass groups were significantly higher than the unoperated group (515 +/- 79 pM x min). The integrated increase in plasma CCK above basal level showed a similar pattern, but the difference between the unoperated and the bypass groups was insignificant.. Postoperative changes in plasma CCK levels neither explain the increased risk of gallstone formation after bypass surgery nor the higher incidence with a long compared to a short ileum left in continuity in the bypass.

Topics: Cholecystokinin; Cholelithiasis; Cross-Sectional Studies; Eating; Fasting; Food; Humans; Jejunoileal Bypass; Obesity, Morbid; Risk Factors

Bariatric procedures that exclude the proximal small intestine lead to significant weight loss which is probably mediated by changes in hormones that alter appetite, such as peptide YY (PYY), ghrelin, cholecystokinin (CCK), and leptin. Here, the effect of the non-surgical duodenal-jejunal bypass liner (DJBL) on concentrations of hormones implicated in appetite control was investigated.. A two-center prospective study was conducted between January and December 2010. Seventeen obese subjects with type 2 diabetes were treated with the DJBL for 24 weeks. Fasting concentrations of leptin and meal responses of plasma PYY, CCK, and ghrelin were determined prior to and after implantation of the DJBL.. At baseline, subjects had an average body weight of 116.0 ± 5.8 kg. One week after implantation, subjects had lost 4.3 ± 0.6 kg (p < 0.01), which progressed to 12.7 ± 1.3 kg at week 24 (p < 0.01). Postprandial concentrations of PYY and ghrelin increased (baseline vs. week 1 vs. week 24 PYY: 2.6 ± 0.2 vs. 4.1 ± 0.4 vs. 4.1 ± 0.7 nmol/L/min and ghrelin: 7.8 ± 1.8 vs. 11.0 ± 1.8 vs. 10.6 ± 1.8 ng/mL/min, all p < 0.05). In parallel, the CCK response decreased (baseline vs. week 1 vs. week 24: 434 ± 51 vs. 229 ± 52 vs. 256 ± 51 pmol/L/min, p < 0.01). Fasting leptin concentrations also decreased (baseline vs. week 24: 98 ± 17 vs. 53 ± 10 ng/mL, p < 0.01).. DJBL treatment induces weight loss paralleled by changes in concentrations of hormones involved in appetite control.

Topics: Bariatrics; Cholecystokinin; Diabetes Mellitus, Type 2; Duodenum; Female; Ghrelin; Humans; Jejunum; Leptin; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Prospective Studies; Treatment Outcome

We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.. Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed by enteroscopy ~10 months later. Mucosal biopsies taken during surgery and enteroscopy were immunohistochemically stained for glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and prohormone convertase 2 (PC2) and the expression of GCG (encoding preproglucagon), PYY, CCK, GIP, GHRL (encoding ghrelin), SCT (encoding secretin), NTS (encoding neurotensin) and NR1H4 (encoding farnesoid X receptor) was evaluated.. The density of cells immunoreactive for GLP-1, CCK and GIP increased in patients after RYGB and the density of those immunoreactive for GLP-1, PYY, CCK and PC2 increased in controls. In both groups, GHRL, SCT and GIP mRNA was reduced after RYGB while PYY, CCK, NTS and NR1H4 gene expression was unaltered. GCG mRNA was upregulated in both groups.. Numerous alterations in the distribution of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of GHRL, SCT and GIP and increased expression of GCG.

Topics: Adult; Cholecystokinin; Diabetes Mellitus, Type 2; Enteroendocrine Cells; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Proprotein Convertase 2; Treatment Outcome

The relation between hunger, satiation, and integrated gastrointestinal motility and hormonal responses in morbidly obese patients after sleeve gastrectomy has not been determined.. The objective was to assess the effects of sleeve gastrectomy on hunger, satiation, gastric and gallbladder motility, and gastrointestinal hormone response after a liquid meal test.. Three groups were studied: morbidly obese patients (n = 16), morbidly obese patients who had had sleeve gastrectomy (n = 8), and nonobese patients (n = 16). The participants fasted for 10 h and then consumed a 200-mL liquid meal (400 kcal + 1.5 g paracetamol). Fasting and postprandial hunger, satiation, hormone concentrations, and gastric and gallbladder emptying were measured several times over 4 h.. No differences were observed in hunger and satiation curves between morbidly obese and nonobese groups; however, sleeve gastrectomy patients were less hungry and more satiated than the other groups. Antrum area during fasting in morbidly obese patients was statistically significant larger than in the nonobese and sleeve gastrectomy groups. Gastric emptying was accelerated in the sleeve gastrectomy group compared with the other 2 groups (which had very similar results). Gallbladder emptying was similar in the 3 groups. Sleeve gastrectomy patients showed the lowest ghrelin concentrations and higher early postprandial cholecystokinin and glucagon-like peptide 1 peaks than did the other participants. This group also showed an improved insulin resistance pattern compared with morbidly obese patients.. Sleeve gastrectomy seems to be associated with profound changes in gastrointestinal physiology that contribute to reducing hunger and increasing sensations of satiation. These changes include accelerated gastric emptying, enhanced postprandial cholecystokinin and glucagon-like peptide 1 concentrations, and reduced ghrelin release, which together may help patients lose weight and improve their glucose metabolism after surgery. This trial was registered at clinicaltrials.gov as NCT02414893.

Topics: Adult; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholecystokinin; Fasting; Female; Gastrectomy; Gastric Emptying; Gastrointestinal Hormones; Gastrointestinal Motility; Ghrelin; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Hunger; Insulin Resistance; Male; Meals; Middle Aged; Obesity, Morbid; Postprandial Period; Satiation

Gastrointestinal hormones are critically involved in the regulation of food intake and body weight. Previous studies support an interplay between gastrointestinal hormones and the serotonergic system. This study explored intestinal neuroendocrine expression patterns in humans with obesity versus nonobese humans.. Jejunum samples were collected from 164 humans with obesity (120 women; BMI (mean ± SD): 43.5 ± 6.6 kg/m(2) ) while they underwent Roux-en-Y gastric bypass surgery and from 18 nonobese humans (7 women; BMI: 23.5 ± 3.0 kg/m(2) ) undergoing distinct intestinal surgeries. mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin1, ghrelin, ghrelin O-acyltransferase (GOAT), leptin, leptin receptor (leptinR), glucagon-like-peptide 1 receptor (GLP1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1), and serotonin receptor 3A (5HT3A R) was determined with qRT-PCR. Ghrelin and GOAT protein expression was quantified using immunohistological stainings. Statistical analyses were performed with SPSS.. Jejunum samples from humans with obesity showed a higher expression of GOAT (mRNA and protein), TPH1, and SERT mRNA compared with the nonobese humans (all P < 0.05). Positive correlations were observed between TPH1, CCK, PYY, and nesfatin1 in nonobese and GOAT, ghrelin, TPH1, SERT, CCK, and PYY in humans with obesity (all P < 0.01).. Our top-down approach substantiates the dysregulation of jejunal neuroendocrine hormones in obesity.

Topics: Acyltransferases; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholecystokinin; Female; Gastric Bypass; Gastrointestinal Hormones; Gene Expression Regulation; Ghrelin; Humans; Jejunum; Leptin; Middle Aged; Neuroendocrine Cells; Obesity, Morbid; Peptide Fragments; Peptide YY; Weight Loss; Young Adult

To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB).. Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender.. Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite.. Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition.. Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Topics: Absorptiometry, Photon; Appetite Regulation; Bile Acids and Salts; Blood Glucose; Body Mass Index; Cholecystokinin; Cross-Sectional Studies; Dumping Syndrome; Energy Metabolism; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Neurotensin; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).. We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.. Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.. Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Topics: Adult; Appetite; C-Peptide; Cholecystokinin; Confounding Factors, Epidemiologic; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Somatostatin; Time Factors; Weight Loss

Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely

Topics: Acylation; Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholecystokinin; Cholesterol, LDL; Fasting; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Morbid; Peptide Hormones; Peptide YY; Poland; Postprandial Period

Maternal obesity has been reported as a risk factor for various maternal and fetal complications. The aim of the present study was to examine the patterns of basal and postprandial plasma concentrations of certain gut hormones affecting food intake such as acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), insulin and glucose in pregnant women with varying body mass gain during physiological pregnancy. The study included 34 women with singleton pregnancies in the 2(nd) trimester of gestation. The examined pregnant women were divided into 4 groups; I. control pregnancy (CP) with weight gain below 0.5 kg/week; II. overweight low weight gain <1 kg/week (OLWG), III. overweight high weight gain >1 kg/week (OHWG); morbidly obese pregnant with weight gain >1.5 kg/week (MOP). The basal acylated-ghrelin levels in MOP subjects were significantly higher than those in CP and no usual suppression of acylated ghrelin after the meal observed in CP as well as in OLWG and OHWG was found in MOP women. Basal PYY(3-36) plasma levels were similar in CP, OLWG and OHWG but in MOP was significantly reduced and no significant increase in hormone level, typically observed in CP, was detected after a meal in overweight or obese women studied. The fasting CCK and C-reactive protein (CRP) levels in MOP subjects were significantly higher than those in CP and other overweight women. In conclusion, we found that pregnant women with overweight and obesity exhibit significant changes in fasting and postprandial gut hormones affecting food intake such as acylated ghrelin, PYY(3-36) and CCK as well as in CRP and these changes might contribute, at least in part, the development of obesity in pregnancy.

Topics: Acylation; Adult; Appetite; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholecystokinin; Fasting; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Homeostasis; Humans; Insulin; Obesity; Obesity, Morbid; Peptide Hormones; Peptide YY; Poland; Postprandial Period; Pregnancy; Pregnancy Complications; Weight Gain

Although cholecystokinin (CCK) is involved in the short-term regulation of satiety, it has not been investigated in obese patients subjected to bariatric restrictive operations.. 8 morbidly obese patients (BMI 49.1 +/- 6.9), 7F and 1M, were investigated before and after vertical banded gastroplasty (VBG). 6 healthy lean volunteers served as the control group. CCK was determined (RIA) after an overnight fast and after the administration of an acidified (pH 3) liquid meal. Blood samples were taken 45 min before the meal, 5 min after it and then every 30 min for 3 hours.. There were no differences between groups in basal CCK levels. However, the peak of CCK after the meal was significantly higher (P <0.01) in obese patients after VBG (24.9 +/- 18 pmol/l) than before VBG (9.8 +/- 6.7 pmol/l) and when compared with the control group (8.0 +/- 6.3 pmol/l). The time needed to reach the peak was longer in healthy volunteers (105 +/- 24.9 min) than in obese patients before VBG (45 +/- 40 min) and after VBG (7.5+/- 12 min) (P<0.01).. VBG increases the peak of CCK secretion and shortens the time to reach it. These changes could contribute to the satiety effects of gastric restrictive operations.

Topics: Adult; Area Under Curve; Cholecystokinin; Female; Gastroplasty; Humans; Male; Middle Aged; Obesity, Morbid; Satiety Response

To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. SIGNIFICANT BACKGROUND DATA: The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes.. Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m (40-53 kg/m) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulin-like growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY).. Changes in mean BMI were rather minimal (43.2 kg/m; P = not significant), but there was a significant decrease in blood glucose (P = 0.005), insulin (P = 0.02), IGF-1 (P < 0.05), leptin (P = 0.001), and an increase in ACTH levels (P = 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P < 0.01), whereas no changes in GIP levels were found in nondiabetics.. Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB.

Topics: Adrenocorticotropic Hormone; Adult; Anastomosis, Roux-en-Y; Biomarkers; Blood Glucose; Body Mass Index; Cholecystokinin; Female; Follow-Up Studies; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Preoperative Care; Probability; Prospective Studies; Sensitivity and Specificity; Somatomedins; Statistics, Nonparametric; Weight Loss

A gastric pacemaker has been developed to treat morbid obesity. Patients experience increased satiety, the ability to reduce food intake, and a resultant weight loss. However, the mechanism behind the changed eating behavior in paced patients is still under investigation.. This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m2) treated with gastric pacing. The peripheral blood levels of satiety signals of cholecystokinin (CCK), somatostatin, glucagon-like peptide-1 (GLP-1), and leptin were studied 1 month before gastric pacer implantation, 1 month after implantation, and 6 months after activation of electrical stimulation. Blood samples were drawn 12 hours after fasting and in response to a hypocaloric meal (270 kcal). Patients were followed monthly for vital signs and weight level.. Gastric pacing resulted in a significant weight loss of a mean of 10.4 kg (4.4 BMI units). No negative side effects or complications were observed during the treatment. After activation of the pacemaker, meal-related response of CCK and somatostatin and basal levels of GLP-1 and leptin were significantly reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01).. Gastric pacing is a novel and promising therapy for morbid obesity. Activation of the gastric pacer was associated with a decrease in plasma levels of CCK, somatostatin, GLP-1, and leptin. More studies are necessary to elucidate the correlations between satiety, weight loss, and digestive neuro-hormone changes.

Topics: Adult; Cholecystokinin; Electric Stimulation Therapy; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Leptin; Male; Obesity, Morbid; Peptides; Satiation; Somatostatin; Stomach; Weight Loss

The risk of developing gallstones is increased in obese subjects. We have investigated whether gallbladder motility in obese subjects is different from that in lean control subjects. In 25 healthy non-diabetic obese subjects and 20 age- and sex-matched lean controls, fasting gallbladder volumes, gallbladder contraction in response to cephalic vagal cholinergic stimulation by modified sham feeding (MSF) and to hormonal stimulation with cholecystokinin (CCK) were studied. Gallbladder volumes were measured during a 30-min MSF period followed 1 h later by a 1-hour continuous i.v. infusion of 0.5 IDU/kg ideal weight of CCK-33. Fasting gallbladder volumes were significantly (p < 0.001) larger in obese (47 +/- 4 cm3) compared to lean subjects (24 +/- 2 cm3). Fasting gallbladder volume was correlated with body mass index (p < 0.01). Gallbladder contraction during MSF was significantly (p < 0.01) reduced in obese (12 +/- 2%) compared to lean subjects (22 +/- 3%). CCK infusion, leading to physiological post-prandial plasma CCK levels, induced a significantly (p < 0.001) greater absolute gallbladder contraction in obese (27 +/- 3 cm3) compared to lean subjects (15 +/- 1 cm3) but the percentage gallbladder contraction was in the same range (64 +/- 3% vs. 67 +/- 4%, respectively). In addition, residual gallbladder volumes after CCK infusion were significantly (p < 0.001) larger in obese (15 +/- 2 cm3) than in lean subjects (7 +/- 1 cm3). Two groups of obese subjects were identified: one with increased (>40 cm3) and one with normal (< or = 40 cm3) fasting gallbladder volumes. Only obese subjects with increased fasting volumes showed abnormal gallbladder motility.

Topics: Adult; Body Mass Index; Cholecystokinin; Fasting; Feeding Behavior; Female; Gallbladder; Gallbladder Emptying; Humans; Infusions, Intravenous; Male; Obesity, Morbid; Risk Factors; Stimulation, Chemical; Ultrasonography; Vagus Nerve

Some studies have shown a more rapid gastric emptying in obese subjects. Six to twelve months after jejunoileal bypass (JIB) neurotensin (NT) and enteroglucagon have been shown to be elevated after food intake. These hormones, together with peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) have been implicated in the reduction of upper gastrointestinal motility seen after infusion of nutrients into the ileum.. To study if the postprandial gut hormone pattern and gastric emptying is altered 20 y after JIB.. Seven subjects operated with JIB a mean (s.d.) 20 +/- 3 y ago, with a BMI of 44 +/- 4 kg/m2 at the time of surgery and 31 +/- 4 at present. For comparison seven sex-matched non-operated obese controls (BMI 43 +/- 3) were studied.. Serial blood samples were obtained every 10 min after intake of a 280 kcal meal. Radioimmunoassays for motilin, cholecystokinin (CCK), NT, PYY and GLP-1 were performed. Gastric emptying of a solid meal was studied using a radioactively labelled omelette (of 310 kcal) for 120 min).. After JIB postprandial motilin, CCK, NT, PYY and GLP-1 were elevated compared to non-operated obese subjects. Similarly, basal levels of CCK, motilin, GLP-1 and PYY were elevated in the operated group. No difference was observed in the rate of gastric emptying between the two groups.. Both fasting and postprandial gut hormone levels are elevated 20 y after JIB. The impact of long-term rapid stimulation of the ileum and subsequent raised gut hormone levels on gastric emptying is not clear.

Topics: Cholecystokinin; Female; Follow-Up Studies; Gastric Emptying; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Jejunoileal Bypass; Male; Middle Aged; Motilin; Neurotensin; Obesity, Morbid; Peptide YY; Peptides; Postprandial Period; Time Factors

The Willmen gastric bubble has been used as an adjunct to weight loss in morbidly obese patients. 35 patients with morbid obesity were studied with routine manometry, esophageal 24-h-pH-measurement, and gastric emptying studies before and 4 weeks after bubble placement. During emptying studies blood samples were taken to measure gastrin, PP, CCK, VIP, neurotensin and insulin. No patient developed heartburn or regurgitation after bubble placement. Esophageal motility and LES function remained unchanged. There was no important pathological gastroesophageal reflux before and after gastric bubble. The gastric emptying time of solid food was unchanged by gastric bubble placement and the emptying time of liquids was accelerated up to normal. In patients with fasting gastrin levels less than 20 pg/ml at the beginning of the first test we found no differences in gastrin release before and after bubble insertion. In patients with primary high fasting values gastrin release was significantly increased. CCK, VIP, neurotensin and insulin levels were unchanged. With PP we measured significantly raised fasting levels after gastric bubble. We conclude that esophageal and LES functions are not altered by Willmen gastric bubble placement and that primary retardation of fluids is changed to normal. Bubble induced gastric tension increases fasting PP. In case of high fasting gastrin the bubble leads to an extremely high food response without any clinical signs.

Topics: Adult; Cholecystokinin; Esophagogastric Junction; Esophagus; Female; Gastric Acidity Determination; Gastric Emptying; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Male; Manometry; Middle Aged; Neurotensin; Obesity, Morbid; Pancreatic Polypeptide; Prostheses and Implants; Vasoactive Intestinal Peptide

The results of our preliminary experience with the gastric balloon program for weight loss in morbidly obese patients are reported. In a pilot project, we measured gastric-acid secretion, gastrin and cholecystokinin (CCK) levels in ten patients before and during balloon therapy in a study of the impact of the balloon on gastric physiology. Gastric-acid secretion tended to decrease following balloon treatment, while gastrin and CCK levels were unchanged suggesting that weight loss is achieved by mechanisms, which are not mediated by gastrin or CCK. The balloon program was then expanded to a group of 29 patients who met the criteria. They were followed for a period of 4 months. Average weight loss for the group was 31 +/- 4 pounds for a monthly average of 8 pounds. The main complications were gastric ulcers in four patients and a small-bowel obstruction in one patient. Satisfactory weight loss was achieved in 80 per cent of patients, but this benefit must be balanced against a relatively high incidence (17%) of side effects, some of which were quite serious. Therefore, the gastric balloon program should still be considered experimental.

Topics: Adult; Body Weight; Cholecystokinin; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Prostheses and Implants