motilin and Obesity

Obesity is a multi-gene syndrome, expression of which is modulated not only by environmental factors but above all by a number of modified genes interacting with each other. Among candidate genes related to obesity phenotype is ghrelin gene. Ghrelin plays a significant role in feeding regulation and is the strongest stimulator of growth hormone secretion. Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor). Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals. Among identificated mutations, two Arg51 Gln and Leu72Met are most often described and change amino-acid sequence of ghrelin (Arg51Gln) and preproghrelin (Leu72Met). Although no direct relationship between Arg51Gln mutation and obesity phenotype was found, it had been shown that carriers of Arg51Gln mutation had significantly decreased plasma ghrelin levels. Furthermore 51Gln allele carriers had higher prevalence of type 2 diabetes mellitus and hypertension than non-carriers. Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity. No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity. The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects. On the other hand, some mutations in preproghrelin gene could be protective against metabolic syndrome.

Topics: Diabetes Mellitus, Type 2; Ghrelin; Humans; Metabolic Syndrome; Motilin; Mutation; Obesity; Peptide Hormones; Polymorphism, Genetic; Receptors, G-Protein-Coupled; Receptors, Ghrelin

Topics: Afferent Pathways; Animals; Bombesin; Brain Mapping; Calcitonin; Calcitonin Gene-Related Peptide; Cholecystokinin; Corticotropin-Releasing Hormone; Disease Models, Animal; Endorphins; Feeding Behavior; Glucagon; Humans; Insulin; Motilin; Nerve Tissue Proteins; Neuropeptide Y; Neurotensin; Obesity; Pancreatic Polypeptide; Satiety Response; Somatostatin; Species Specificity; Stress, Psychological; Taste; Thyrotropin-Releasing Hormone

Topics: Cholecystokinin; Diabetes Mellitus, Type 2; Digestive System Physiological Phenomena; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Motilin; Neurotensin; Obesity; Pancreatic Polypeptide; Pentagastrin; Secretin; Somatostatin; Vasoactive Intestinal Peptide

Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores.. Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire.. Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores.. Motilin may be an important regulator involved in the pathogenesis of obesity.

Topics: Adult; Case-Control Studies; Duodenum; Erythromycin; Female; Gastric Bypass; Gastrointestinal Agents; Ghrelin; Humans; Hunger; Male; Motilin; Myoelectric Complex, Migrating; Obesity; Postoperative Period; Preoperative Period; Pyloric Antrum; Surveys and Questionnaires

Topics: Gastric Bypass; Humans; Hunger; Motilin; Obesity

The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin.. [(125)I]-motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in CHO cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (EFS) of intrinsic nerves.. Azithromycin (1-100 μM) and erythromycin (3-30 μM) concentration-dependently displaced [(125)I]-motilin binding to the motilin receptor (52 ± 7 and 58 ± 18% displacement at 100 and 30 μM respectively). Azithromycin, erythromycin and motilin concentration-dependently caused short-lived increases in intracellular [Ca(2+)] in cells expressing the motilin receptor. EC50 values were, respectively, 2.9, 0.92 and 0.036 μM (n = 3 each); and maximal activities were similar. In human stomach, EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30-300 μM each) facilitated these contractions (apparent E(max) values of 2007 ± 396 and 1924 ± 1375%, n = 3-4 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short-lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug.. Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long-lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic activity of azithromycin.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Azithromycin; Calcium; CHO Cells; Cricetulus; Electric Stimulation; Erythromycin; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Male; Middle Aged; Motilin; Obesity; Pyloric Antrum; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Recombinant Proteins

To investigate the preproghrelin gene for variants and their association with obesity and type 2 diabetes.. 82 obese probands were analyzed for mutations using single-strand conformational polymorphism, heteroduplex analyses and sequencing. Association studies were performed in 234 juvenile-onset obese and 323 lean men and in 557 type 2 diabetic and 233 glucose tolerant subjects.. We identified two novel variants, 36C > T and IVS3 + 715delC, and 4 known variants, Arg51Gln, Leu72Met, Gln90Leu, and IVS1 + 169G > A. None of the variants showed any significant association with obesity or type 2 diabetes or estimates of glucose and lipid metabolism in glucose tolerant subjects.. Variation in the preproghrelin gene is not associated with juvenile-onset obesity, type 2 diabetes or related phenotypes among the examined Danish Caucasian subjects.

Topics: Adolescent; Adult; Case-Control Studies; Cohort Studies; Denmark; Diabetes Mellitus, Type 2; DNA Mutational Analysis; Female; Genotype; Ghrelin; Humans; Male; Middle Aged; Motilin; Obesity; Polymorphism, Genetic

Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

Topics: Body Mass Index; Child; Cholesterol; Female; Genetic Carrier Screening; Ghrelin; Humans; Korea; Leucine; Male; Methionine; Motilin; Obesity; Polymorphism, Genetic; Triglycerides

Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P = 0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P = 0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.

Topics: Body Height; Body Weight; Child; Child, Preschool; Ghrelin; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Motilin; Obesity; Peptide Hormones; Peptides; Polymerase Chain Reaction; Polymorphism, Single Nucleotide

Topics: Gastrointestinal Motility; Humans; Motilin; Obesity; Pancreatic Polypeptide

A number of human diseases with intestinal adaptation have been investigated, including acute infective diarrhoea, intestinal resection, jejuno-ileal bypass, coeliac disease, tropical sprue, chronic pancreatitis and cystic fibrosis. In all, the newly isolated hormone enteroglucagon appeared to be elevated in proportion to the degree of adaptation. In rats after gut resection and cold adaptation, enteroglucagon was also elevated and the degree of elevation correlated closely with the crypt cell production rate (CCPR). Chronic administration of somatostatin suppressed both enteroglucagon and CCPR, while bombesin stimulated both. A crude preparation of enteroglucagon was found to directly stimulate DNA synthesis in enterocyte cultures. It is thus concluded that, at present, the most likely candidate for the humoral component of intestinal adaptation is the hormonal peptide enteroglucagon.

Topics: Adaptation, Physiological; Adult; Animals; Cattle; Diarrhea; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Hypertrophy; Infant; Inflammation; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Intestines; Mice; Motilin; Obesity; Rats

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 placed 50 cm proximal to the ileocecal value. Pancreatic polypeptide (PP) and motilin fasting and meal-stimulated plasma concentrations were determined in 13 nonobese healthy volunteers, in 13 nonoperated obese patients, in 9 subjects within two months, in 12 subjects four to twelve months, and in 7 subjects fifteen to twenty months after operation. There were no significant differences in PP fasting levels between either the obese and control groups or between the postoperative groups and the preoperative group. Both meal-stimulated peak and integrated response values were similar in the obese and control groups, and were strikingly and progressively reduced postoperatively, with statistically significant difference between all postoperative groups and preoperative group. Mean plasma motilin fasting and peak values were higher in the obese group than in the control group, and significantly reduced in the 4-12 and 15-20 month group. Despite the huge variability among data, the integrated response in the 0-2 month group was significantly decreased in comparison with the preoperative group, while a subsequent progressive increase was shown by the 4-12 and 15-20 month groups.

Topics: Fasting; Follow-Up Studies; Gastrointestinal Hormones; Humans; Ileum; Motilin; Obesity; Pancreatic Polypeptide; Stomach; Time Factors