leptin and Gastritis

To evaluate the influence of Helicobacter pylori infection on the gastric regulation of food intake and body weight.. H. pylori infection leads to a decrease of circulating ghrelin through a reduction of ghrelin-producing cells in the gastric mucosa and increases the amount of gastric leptin with no effect on circulating leptin levels. Eradication of H. pylori reverses the abnormal regulation of gastric hormone secretion. This finding is suggested to favor weight gain after H. pylori eradication and points to the potential effect of H. pylori in the pathophysiology of obesity.. H. pylori has an influence on the release of gastric hormones and therefore plays a role in the regulation of body weight, hunger and satiety.

Topics: Appetite; Body Weight; Eating; Gastric Mucosa; Gastritis; Ghrelin; Helicobacter Infections; Helicobacter pylori; Homeostasis; Humans; Leptin

Topics: Animals; Body Mass Index; Body Weight; Female; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Mice; Obesity; Pepsinogens; Rats

Topics: Animals; Gastric Acid; Gastric Mucosa; Gastritis; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Lipid Metabolism; Nitric Oxide; Peptide Hormones; Stomach Diseases

The recent discovery of gastric leptin has initiated several investigations on the possible role of leptin in digestive physiology. The following clues are currently suggested: leptin might control meal size in cooperation with Cholecystokinin, help cytoprotection of the gastric mucosa, play a role in gut inflammatory processes, regulate secretion of gastric hormones such as gastrin and somatostatin, and modulate intestinal transport of small peptides. The present review is a brief survey of the most significant advances in these issues.

Topics: Animals; Appetite Regulation; Biological Transport; Cholecystokinin; Cytoprotection; Gastric Mucosa; Gastrins; Gastritis; Humans; Leptin; Peptides; Somatostatin

Cold Syndrome and Hot Syndrome are thousand-year-old key therapeutic concepts in traditional Chinese medicine (TCM), which depict the loss of body homeostasis. However, the scientific basis of TCM Syndrome remains unclear due to limitations of current reductionist approaches. Here, we established a network balance model to evaluate the imbalanced network underlying TCM Syndrome and find potential biomarkers. By implementing this approach and investigating a group of chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG) patients, we found that with leptin as a biomarker, Cold Syndrome patients experience low levels of energy metabolism, while the CCL2/MCP1 biomarker indicated that immune regulation is intensified in Hot Syndrome patients. Such a metabolism-immune imbalanced network is consistent during the course from CSG to CAG. This work provides a new way to understand TCM Syndrome scientifically, which in turn benefits the personalized medicine in terms of the ancient medicine and complex biological systems.

Topics: Adult; Biomarkers; Chemokine CCL2; Chronic Disease; Cluster Analysis; Diagnosis, Differential; Energy Metabolism; Female; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Gene Expression Profiling; Gene Regulatory Networks; Humans; Immunity; Immunohistochemistry; Inflammation; Leptin; Male; Medicine, Chinese Traditional; Middle Aged; Models, Genetic; Principal Component Analysis; Syndrome

To investigate serum ghrelin and leptin levels in relation to pathology change of gastric mucous membrane and body mass index (BMI).. A total of 156 patients were studied from Apr. 2009 to Jul. 2009. Blood serum ghrelin and leptin levels were assessed by ELISA method. All patients underwent gastroscopy with biopsies from gastric antrum and gastric body in order to evaluate pathology change of gastric mucous membrane.. Serum ghrelin levels (250.14 ng/L vs 386.65 ng/L) and leptin levels (4.12 μg/L vs 4.31 μg/L) in male subjects were lower than in female ones. There was significant difference in ghrelin levels (P=0.003), but not in leptin levels (P=0.681). ghrelin levels in ≤35-year-old group, 36 to 54-year-old group and ≥55-year-old group were 408.93 ng/L, 309.16 ng/L and 236.76 ng/L respectively, with significant difference (P=0.007). While leptin levels in ≤35-year-old group, 36 to 54-year-old group and ≥55-year-old group were 4.26 μg/L, 4.41 μg/L and 3.86 μg/L respectively, without significant difference (P=0.549). Serum ghrelin levels (308.40 ng/L vs 344.88 ng/L) and leptin levels (4.17 μg/L vs 4.35 μg/L) were both lower in chronic superficial gastritis patients than in chronic atrophy gastritis patients. But no statistically significant difference of ghrelin and leptin levels emerged either in chronic superficial gastritis group or in chronic atrophy gastritis group (P=0.870 and 0.436, respectively). There was a negative correlation between ghrelin and BMI (P=0.000), but a positive correlation between leptin and BMI (P=0.000).. Gender and age have influence on serum ghrelin levels. Meanwhile, serum ghrelin and leptin levels were associated with neither chronic superficial gastritis nor chronic atrophy gastritis. Serum ghrelin levels decrease and leptin levels increase with the increase of BMI.

Topics: Adolescent; Adult; Aged; Biopsy; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastritis; Gastroscopy; Ghrelin; Humans; Leptin; Male; Middle Aged; Young Adult

Bacterial infection can trigger the development of functional GI disease. Here, we investigate the role of the gut-brain axis in gastric dysfunction during and after chronic H. pylori infection. Control and chronically H. pylori-infected Balb/c mice were studied before and 2 mo after bacterial eradication. Gastric motility and emptying were investigated using videofluoroscopy image analysis. Gastric mechanical viscerosensitivity was assessed by cardioautonomic responses to distension. Feeding patterns were recorded by a computer-assisted system. Plasma leptin, ghrelin, and CCK levels were measured using ELISA. IL-1beta, TNF-alpha, proopiomelanocortin (POMC), and neuropeptide Y mRNAs were assessed by in situ hybridizations on frozen brain sections. Gastric inflammation was assessed by histology and immunohistochemistry. As shown previously, H. pylori-infected mice ate more frequently than controls but consumed less food per bout, maintaining normal body weight. Abnormal feeding behavior was accompanied by elevated plasma ghrelin and postprandial CCK, higher TNF-alpha (median eminence), and lower POMC (arcuate nucleus) mRNA. Infected mice displayed delayed gastric emptying and visceral hypersensitivity. Eradication therapy normalized gastric emptying and improved gastric sensitivity but had no effect on eating behavior. This was accompanied by persistently increased TNF-alpha in the brain and gastric CD3(+) T-cell counts. In conclusion, chronic H. pylori infection in mice alters gastric emptying and mechanosensitivity, which improve after bacterial eradication. A feeding pattern reminiscent of early satiety persists after H. pylori eradication and is accompanied by increased TNF-alpha in the brain. The results support a role for altered gut-brain pathways in the maintenance of postinfective gut dysfunction.

Topics: Animals; Autonomic Nervous System; Brain; CD3 Complex; Cell Count; Feeding Behavior; Female; Gastritis; Gastrointestinal Motility; Gastrointestinal Tract; Ghrelin; Heart Rate; Helicobacter Infections; Helicobacter pylori; In Situ Hybridization; Leptin; Mice; Mice, Inbred BALB C; Receptors, Cholecystokinin

Helicobacter pylori, and the chronic gastric inflammation that it causes, may compromise the function and survival of ghrelin-producing cells, resulting in a decrease of circulating ghrelin levels. This finding raises the possibility that the infection might affect growth in children by reducing the ghrelin production.. To determine baseline circulating levels of ghrelin and leptin in prepubertal children with and without H. pylori infection and to evaluate the long-term effects of H. pylori eradication on circulating levels of ghrelin and leptin as well as on body composition.. Thirty children with H. pylori-associated gastritis, 35 children with H. pylori-negative gastric mucosa, and 20 healthy controls were studied.. At baseline, while leptin levels were significantly lower in H. pylori-positive patients, ghrelin concentrations did not differ among the three study groups. However, a significant inverse correlation between ghrelin concentrations and histological severity of gastritis was found. Eradication of the organism was associated with a progressive decrease in ghrelin concentrations over baseline at both 6- and 12-month follow-ups. SDS-body mass index (BMI), lean and fat mass, as well as leptin concentrations, significantly increased over baseline at both follow-ups.. In prepubertal children, serum ghrelin concentrations are inversely related to the severity of H. pylori-associated gastritis. In these youngsters, long-term eradication of H. pylori infection is associated with a significant increase in BMI, lean and fat mass along with a significant decrease in circulating ghrelin levels and an increase in leptin levels.

Topics: Anti-Bacterial Agents; Body Composition; Body Mass Index; Child; Child Development; Child, Preschool; Female; Follow-Up Studies; Gastritis; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Insulin-Like Growth Factor I; Leptin; Male

A vaccine against Helicobacter pylori would be a desirable alternative to antibiotic therapy. Vaccination has been shown to be effective in animal models but the mechanism of protection is poorly understood. Previous studies investigating the gene expression in stomachs of vaccinated mice showed changes in adipokine expression correlated to a protective response. In this study, we investigate a well-characterized adipokine-leptin, and reveal an important role for leptin receptor signaling in vaccine-induced protection.. Leptin receptor signaling-deficient (C57BL/Ks Lepr(db)), wild-type C57BL/Ks m littermates and C57BL/6 mice were vaccinated, and then challenged with H. pylori. Levels of bacterial colonization, antibody levels, and gastric infiltrates were compared. The local gene expression pattern in the stomach of leptin receptor signaling-deficient and wild-type mice was also compared using microarrays.. Interestingly, while vaccinated wild-type lean C57BL/6 and C57BL/Ks m mice were able to significantly reduce colonization compared to controls, vaccinated obese C57BL/Ks Lepr(db) were not. All mice responded to vaccination, i.e. developed infiltrates predominantly of T lymphocytes in the gastric mucosa, and made H. pylori-specific antibodies. A comparison of expression profiles in protected C57BL/6 and nonprotected C57BL/Ks Lepr(db) mice revealed a subset of inflammation-related genes that were more strongly expressed in nonprotected mice.. Our data suggest that functional leptin receptor signaling is required for mediating an effective protective response against H. pylori.

Topics: Animals; Bacterial Vaccines; Gastritis; Helicobacter Infections; Helicobacter pylori; Leptin; Mice; Mice, Inbred C57BL; Microarray Analysis; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction

The purpose of this study was to examine the changes in gastric ghrelin and leptin with respect to Helicobacter pylori infection and whether such changes affect the plasma levels of leptin and ghrelin. In addition, we examined the relationship between changes in gastric mucosal ghrelin and leptin levels and gastrointestinal symptoms. Sixty-three patients diagnosed with chronic gastritis were enrolled in the study. Twenty-nine patients were Helicobacter pylori negative and 34 were Helicobacter pylori positive. Expression of ghrelin and leptin mRNA in the gastric mucosa was measured using endoscopic biopsies from the fundus. Plasma levels of ghrelin and leptin were measured by radioimmunoassay. Expression of leptin mRNA in the gastric mucosa was significantly higher in Helicobacter pylori-positive patients than in negative patients (0.38 +/- 0.17 vs. 0.24 +/- 0.12, p = 0.039). The expression of ghrelin was lower in positive patients than in the negative group, although this difference was not significant (p = 0.07). However, there was no significant difference in plasma leptin and ghrelin levels. Gastric mucosal ghrelin mRNA expression was significantly lower in patients with dyspepsia than in those without (0.15 +/- 0.11 vs. 0.23 +/- 0.20, p = 0.05). Helicobacter pylori infection and gastrointestinal symptoms could be associated with leptin and ghrelin expression in the gastric mucosa.

Topics: Adult; Aged; Biomarkers; Biopsy; Diagnosis, Differential; Female; Gastric Mucosa; Gastritis; Gastroscopy; Gene Expression; Ghrelin; Growth Hormone; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Middle Aged; Peptide Hormones; Polymerase Chain Reaction; Prognosis; Radioimmunoassay; RNA, Messenger; Severity of Illness Index; Surveys and Questionnaires

Recently, gastric Helicobacter pylori (H. pylori) colonization has been shown to affect the expression of leptin and ghrelin, hormones that control appetite and satiety. Gastric leptin, produced by chief and parietal cells and released in response to meals, may play a role in weight gain after eradication of H. pylori infection, whereas ghrelin, produced by X/A-like enteroendocrine cells in oxyntic gland, is released during fasting, and suppressed by feeding and leptin. Whether either that H. pylori genes represent microbial contributions to the complement of thrifty genes of humans, or that H. pylori disappearance plays a role in adiposity remains to be determined. Simply, ghrelin-leptin might tango in body weight regulation, gastric inflammation, and gastric motility. In the current review about the possible role of ghrelin in gastric inflammation, we found that high serum albumin condition decreased ghrelin expression, whereas serum albumin deprivation significantly increased ghrelin expression, however, of which regulation was abolished after H. pylori infection. Ghrelin significantly attenuated the inflammatory stimuli imposed after H. pylori, shown with inactivation of phospho-extracellular signal-regulated kinase (p-ERK) and nuclear factor-kappaB (NF-kappaB)-DNA binding activities. Conclusively, besides orexigenic and weight gaining actions of gastric hormone, ghrelin, it likely endows the stomach the protective effect from exogenous damages.

Topics: Amino Acid Sequence; Appetite Stimulants; Gastritis; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Insulin-Like Growth Factor I; Leptin; Mitogen-Activated Protein Kinases; Molecular Sequence Data; Neurosecretory Systems; NF-kappa B; Peptide Hormones; Signal Transduction; Weight Gain

The gp130(757F/F) mouse is a well-characterized and robust model of distal gastric tumorigenesis displaying many of the characteristics of human intestinal type gastric cancer. Key to the development of tumors in this model, and in many examples of human tumor development, is hyperactivation of the transcription factor STAT3. This study addressed the requirement for STAT3 activation in tumor initiation and characterized some of the genes downstream of STAT3 required for tumor development. Furthermore, the interaction among STAT3, the microbial environment, and tumorigenesis was evaluated.. The role of STAT3 in gastric tumor development was assessed in detail in gp130(757F/Y757F):STAT3(+/-) mice displaying reduced STAT3 activity. Tumor size was quantified morphologically, and the effects on endocrine cell populations, neovascularization, and inflammatory cell infiltration as well as the outcome of STAT3 activation on transcription of a number of genes relevant in growth and inflammation were quantified.. Loss of one STAT3 allele in gp130(757F/F) mice reduced the frequency and rate of tumor development because of inhibition of proliferation-induced glandular hyperplasia. There was also a concomitant reduction in the degree of inflammatory infiltration and cytokine and chemokine expression, angiogenesis, and expression of metalloproteinases and growth factors. Antimicrobial treatment of gp130(757F/F) mice slowed tumor growth coincident with reduced macrophage and neutrophil infiltration.. Activation of STAT3 and the microbial environment are pivotal for gastric tumor initiation and development in the gp130(757F/F) mouse, thus supporting the notion that STAT3 activation may play a role in human gastric cancer development.

Topics: Animals; Cell Division; Cell Movement; Cytokine Receptor gp130; Disease Models, Animal; Extracellular Matrix; Gastric Mucosa; Gastrins; Gastritis; Gene Expression Regulation, Neoplastic; Leptin; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neovascularization, Pathologic; Neutrophils; Phosphorylation; Pyloric Antrum; Somatostatin; STAT3 Transcription Factor; Stomach Neoplasms

To determine the concentrations of leptin in plasma and gastric fundic mucosa in humans, with reference to Helicobacter pylori (H pylori) infection, and their association with gastric mucosal levels of interleukin (IL)-1beta, IL-6 and IL-8.. Plasma leptin concentrations were determined in 135 outpatients with non-ulcer dyspepsia, consisting of 95 H pylori-infected and 40 uninfected subjects, and 13 patients before and after cure of the infection with anti-H pylori regimen. Using biopsy samples that were endoscopically obtained from the middle corpus along the greater curvature, gastric leptin contents were measured by radioimmunoassay and the mucosal concentrations of IL-1beta, IL-6 and IL-8 were measured by enzyme linked immunosorbent assay. We also analysed the expression of leptin in the fundic mucosa by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry.. The mucosal levels of leptin in the fundic mucosa of H pylori-infected patients were significantly higher than those of uninfected patients. The amount of gastric leptin correlated positively with the mucosal levels of IL-1beta and IL-6, but not IL-8. Circulating leptin correlated with body mass index, but not with H pylori status, and there was no change in plasma leptin levels following cure of the infection. Leptin immunoreactive cells were noted in the lower half of the fundic glands, and its expression of messenger ribonucleic acid in the oxyntic mucosa was detected by RT-PCR.. Leptin production is enhanced in H pylori-infected gastric mucosa. Gastric leptin may be involved in immune and inflammatory response during H pylori infection, through interaction with proinflammatory cytokines.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastric Fundus; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; RNA, Messenger

Leptin, a multifunctional hormone that regulates food intake and energy expenditure, has emerged recently as an important modulator of gastric mucosal responses to Helicobacter pylori infection. We applied the animal model of H. pylori LPS-induced gastritis to investigate the role of endothelin-1 (ET-1) in the mucosal leptin production. We show that the histologic pattern of inflammation reached a maximum on the fourth day following the LPS and was reflected in a marked increase in the mucosal level of ET-1 and leptin. Therapeutic administration of phosphoramidon, an inhibitor of ECE-1 activity, led to a 61.2% decline in the mucosal ET-1 level and a 64.1% reduction in leptin, while the severity of mucosal inflammatory involvement increased by 28.6%. A drop in the level of leptin and the increase in severity of the inflammatory involvement elicited by the LPS was also attained in the presence of ET(A) receptor antagonist BQ610, but not the ET(B) receptor antagonist BQ788. Moreover, administration of ERK inhibitor, PD98059, in the presence of ET(B) receptor antagonist, but not the ET(A) receptor antagonist, caused reduction in the mucosal leptin level. Our findings are the first to implicate ET-1 as a key factor in up-regulation of gastric mucosal leptin-associated H. pylori infection. We also show that the effect of ET-1 on leptin production is a consequence of ET(A) receptor activation.

Topics: Animals; Aspartic Acid Endopeptidases; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Endothelin-Converting Enzymes; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Gastric Mucosa; Gastritis; Glycopeptides; Helicobacter pylori; Leptin; Lipopolysaccharides; Metalloendopeptidases; Oligopeptides; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Up-Regulation

Topics: Adolescent; Anti-Bacterial Agents; Body Mass Index; Child; Drug Therapy, Combination; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male

Topics: Abomasum; Animals; Appetite; Cattle; Cattle Diseases; Gastrins; Gastritis; Host-Parasite Interactions; Leptin; Neuropeptide Y; Sheep; Sheep Diseases

Leptin, a newly discovered weight-reducing hormone, is mainly produced in fat cells. Recently, this hormone has been reported to be produced in rat gastric mucosa cells. In the present study we analyzed the localization and expression of leptin and its receptors in normal human gastric mucosa and in patients with Helicobacter pylori-associated gastritis.. Plasma leptin levels and gastric mucosa leptin content were determined in 39 patients with dyspepsia. Cellular localization of leptin and of the signaling receptor (Ob-RL) were assessed by immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) for leptin receptor isoforms was performed on gastric epithelial cells isolated by laser-capture-microdissection.. Leptin content of the corpus gastric mucosa in H. pylori-positive patients was significantly increased (4.6+/-1.2. n = 15) as compared with the H. pylori-negative group (27.5+/-0.5 pg/mg, n = 24, P = 0.006). The presence of leptin immunoreactivity was shown in the lower half of corpus epithelial glands. By RT-PCR no leptin mRNA was detectable in human gastric tissue. In contrast, expression of both Ob-R(L) and the leptin receptor isoforms could be detected in gastric epithelial cells. Leptin receptor protein was detected throughout the mucosa.. Leptin itself is stored and secreted but not produced in human gastric mucosa. The functional receptor and all isoforms are present in human gastric mucosa. H. pylori-associated gastritis leads to significant increases in local leptin concentration in the gastric corpus.

Topics: Analysis of Variance; Biopsy; Carrier Proteins; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Leptin; Male; Middle Aged; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA