leptin and Irritable-Bowel-Syndrome

Alterations in gut endocrine cells and hormone levels have been measured in patients with irritable bowel syndrome (IBS). The hypothesis of the present study was that hormone levels would change after 4 weeks of a starch- and sucrose-reduced diet (SSRD) intervention corresponding to decreased carbohydrate intake and symptoms. Among 105 IBS patients from primary and tertiary healthcare, 80 were randomized to SSRD, while 25 followed their ordinary diet. Food diaries, Rome IV, and IBS-symptom severity score (IBS-SSS) questionnaires were completed, and blood samples were collected at baseline and after the intervention. Serum C-peptide, gastric inhibitory peptide, glucagon, glucagon-like peptide-1, insulin, leptin, luteinizing hormone, polypeptide YY, and glucose were measured, along with the prevalence of autoantibodies against gonadotropin-releasing hormone; its precursor, progonadoliberin-2, and receptor; and tenascin C. Carbohydrate intake was lower in the intervention group than in controls at week 4 (median: 88 [66-128] g vs 182 [89-224] g; P < .001). The change in carbohydrate intake, adjusted for weight, was associated with a decrease in C-peptide (β: 14.43; 95% confidence interval [CI]: 4.12-24.75) and insulin (β: 0.18; 95% CI: 0.04-0.32) levels. Glucose levels remained unchanged. The IBS-SSS scores were lower in the intervention group but not in controls (P < .001), without any association with changes in hormone concentrations. There was no difference in autoantibody prevalence between patients and healthy controls. In conclusion, the hypothesis that reduced carbohydrate intake corresponded to altered hormonal levels in IBS was accepted; however, there was no relationship between hormonal concentrations and symptoms.

Topics: Adult; C-Peptide; Diet, Carbohydrate-Restricted; Female; Humans; Insulin; Irritable Bowel Syndrome; Leptin; Male; Middle Aged; Severity of Illness Index

OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Celiac Disease; Diarrhea; Diet, Gluten-Free; Female; Genetic Markers; Humans; Interleukin-6; Interleukin-8; Irritable Bowel Syndrome; Leptin; Linear Models; Longitudinal Studies; Male; Middle Aged; Polymorphism, Single Nucleotide; Resistin; Treatment Outcome

The aim of this study was to assess the nutritional status and serum concentrations of adipokines in children with irritable bowel syndrome (IBS) and healthy controls. We also sought to evaluate their relation to metabolic parameters.. We studied 33 IBS patients (11 girls, 22 boys) aged 5-17 years and 30 healthy age-matched controls (11 girls, 19 boys). The analysis included anthropometric measurements, body composition parameter measurements using bioimpedance, and biochemical tests and measurements of serum concentrations of leptin, adiponectin, chemerin, and omentin-1.. The results of the anthropometric measurements were comparable between the patients and the controls. The patients had higher triglycerides, HOMA-IRs, and chemerin concentrations than the healthy subjects. The HDL cholesterol and omentin-1 levels were lower than in the controls. Leptin and adiponectin did not differ significantly between the groups. An analysis of the receiver operator curves (ROCs) showed that serum concentrations of chemerin ≥ 232.8 ng/mL had 30% sensitivity and 87% specificity when they were used to differentiate between children with IBS and healthy subjects. In the case of serum omentin-1 concentrations ≤ 279.4 ng/mL, the sensitivity and specificity were 60% and 80%, respectively.. The nutritional status of children with IBS did not differ from that of the healthy controls. We found significant differences in serum chemerin and omentin-1 concentrations between IBS patients and healthy children. These adipokines could be used as IBS biomarkers as they demonstrate good specificity and moderate sensitivity. The serum concentrations of chemerin and omentin-1 in IBS patients were related to nutritional status and insulin resistance.

Topics: Adipokines; Adiponectin; Adolescent; Chemokines; Child; Child, Preschool; Cytokines; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Irritable Bowel Syndrome; Leptin; Male; Nutritional Status

Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition predominantly affecting the female sex, and is characterized by brain-gut axis dysregulation. Relevance of hormones along the hypothalamic-pituitary gonadal axis and hypothalamic-pituitary adrenal axis to IBS symptomatology remain unclear, as does the significance of other modulators including brain derived neurotrophic factor (BDNF), leptin, and transforming growth factor βeta 1 (TGF-β1).. Females with IBS were compared with female healthy controls (HC) on age, race, hormonal contraceptive use, body mass index, adrenocorticotropic hormone, cortisol, estradiol, follicular stimulating hormone, luteinizing hormone, progesterone, total cholesterol, Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS). BDNF, leptin, and TGF-β1 were quantified using enzyme-linked immunosorbent assay. Descriptive statistics, non-parametric techniques, and regression analyses were performed.. Participants with IBS (n = 12) displayed higher estradiol (. Elevated estradiol in participants with IBS, and differential patterns of biological and psychological indices between groups, encourages further inquiry on the relevance of sex hormones, BDNF, leptin, and TGF-β1 to symptoms of IBS. Future research endeavors should conduct longitudinal quantification of sex hormones with subjective symptom assessment to facilitate insight on the pathophysiology and female sex bias in IBS.

Topics: Adrenocorticotropic Hormone; Adult; Brain-Derived Neurotrophic Factor; Depression; Female; Gonadal Steroid Hormones; Humans; Hydrocortisone; Irritable Bowel Syndrome; Leptin; Pilot Projects; Transforming Growth Factor beta1

Obesity and irritable bowel syndrome (IBS) are two major public health issues. Interestingly previous data report a marked increase of IBS prevalence in morbid obese subjects compared with non-obese subjects but underlying mechanisms remain unknown. Obesity and IBS share common intestinal pathophysiological mechanisms such as gut dysbiosis, intestinal hyperpermeability and low-grade inflammatory response. We thus aimed to evaluate the link between obesity and IBS using different animal models. Male C57Bl/6 mice received high fat diet (HFD) for 12 weeks and were then submitted to water avoidance stress (WAS). In response to WAS, HFD mice exhibited higher intestinal permeability and plasma corticosterone concentration than non-obese mice. We were not able to reproduce a similar response both in ob/ob mice and in leptin-treated non-obese mice. In addition, metformin, a hypoglycemic agent, limited fasting glycaemia both in unstressed and WAS diet-induced obese mice but only partially restored colonic permeability in unstressed HFD mice. Metformin failed to improve intestinal permeability in WAS HFD mice. Finally, cecal microbiota transplantation from HFD mice in antibiotics-treated recipient mice did not reproduce the effects observed in stressed HFD mice. In conclusion, stress induced a more marked intestinal barrier dysfunction in diet-induced obese mice compared with non-obese mice that seems to be independent of leptin, glycaemia and gut microbiota. These data should be further confirmed and the role of the dietary composition should be studied.

Topics: Animals; Cecum; Colon; Corticosterone; Diet, High-Fat; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Intestinal Mucosa; Irritable Bowel Syndrome; Leptin; Male; Metformin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Permeability; Prevalence; Stress, Physiological

To measure the leptin levels in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and analyze the relationship of leptin with clinical features, visceral sensitivity, mast cells, and nerve fibers.. Forty-two patients with IBS-D fulfilling the Rome III criteria and 20 age- and sex-matched healthy controls underwent clinical and psychological evaluations using validated questionnaires (including IBS Symptom Severity Scale, IBS-specific Quality of Life, Hamilton Anxiety Scale, and Hamilton Depression Scale), along with colonoscopy, colonic mucosal biopsy, and visceral sensitivity testing. Serum leptin levels were assayed using enzyme-linked immunosorbent assay. Mucosal leptin expression and localization were evaluated using immunohistochemistry and immunofluorescence. Mucosal leptin mRNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction. Mast cell counts and activation rates were investigated by toluidine blue staining. Correlation analyses between these parameters were performed.. There were no statistically significant differences in age, gender, or body mass index between the IBS-D group and the control group. The median IBS Symptom Severity Scale score in the IBS-D group was 225.0 (range, 100-475). IBS-D patients had significantly increased anxiety [IBS-D: median, 6.5; interquartile range (IQR), 3.3; control: median, 2.0; IQR, 2.0;. Increased levels of mucosal leptin may interact with mast cells and the nervous system to contribute to the pathogenesis of IBS-D.

Topics: Adult; Biomarkers; Case-Control Studies; Diarrhea; Enteric Nervous System; Female; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Leptin; Male; Mast Cells; Receptors, Leptin; RNA, Messenger; Up-Regulation; Young Adult

Alterations of the small-intestinal permeability (s-IP) might play an essential role in a subgroup of diarrhoea-predominant IBS (D-IBS) patients.. (. The study included 34 D-IBS patients and 17 healthy controls (HC). s-IP permeability was assayed by high-performance liquid chromatography determination in the urine of the lactulose to mannitol ratio. Concentrations of IL-6, IL-8, TNF-. D-IBS(-) patients had a significantly higher GSRS cluster pain and diarrhoea profile than D-IBS(+) ones. Significant correlations were found between the symptoms clusters and immune activation and inflammation markers. The levels of adipo(cyto)kines in D-IBS(+) patients were higher than those of controls, and IL-6 levels correlated with those of LPS. Leptin and BDNF were significantly higher, and neurotensin levels were significantly lower in D-IBS(+) than in controls. No differences were found in the frequency distribution of genotypes among the study groups.. Results from this study could be of some help in the characterization of the D-IBS and highlight the contribution of an altered intestinal barrier in the pathogenesis of this syndrome. Besides, a role could be ascribed to molecules secreted by the visceral adipose tissue that can impact on barrier functions.

Topics: Adipose Tissue; Adult; Biomarkers; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cytokines; Diarrhea; Female; Humans; Intestine, Small; Irritable Bowel Syndrome; Leptin; Male; Polymorphism, Single Nucleotide

What is the central question of this study? Does crosstalk exist between leptin and interleukin-6 in colonic enteric neurons, and is this a contributory factor in gastrointestinal dysfunction associated with irritable bowel syndrome? What is the main finding and its importance? Leptin ameliorates the prosecretory and prokinetic effects of the pro-inflammatory cytokine interleukin-6 on rat colon. Leptin also suppresses the neurostimulatory effects of irritable bowel syndrome plasma, which has elevated concentrations of interleukin-6, on enteric neurons. This may indicate a regulatory role for leptin in immune-mediated bowel dysfunction. In addition to its role in regulating energy homeostasis, the adipokine leptin modifies gastrointestinal (GI) function. Indeed, leptin-resistant obese humans and leptin-deficient obese mice exhibit altered GI motility. In the functional GI disorder irritable bowel syndrome (IBS), circulating leptin concentrations are reported to differ from those of healthy control subjects. Additionally, IBS patients display altered cytokine profiles, including elevated circulating concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6), which bears structural homology and similarities in intracellular signalling to leptin. This study aimed to investigate interactions between leptin and IL-6 in colonic neurons and their possible contribution to IBS pathophysiology. The functional effects of leptin and IL-6 on colonic contractility and absorptosecretory function were assessed in organ baths and Ussing chambers in Sprague-Dawley rat colon. Calcium imaging and immunohistochemical techniques were used to investigate the neural regulation of GI function by these signalling molecules. Our findings provide a neuromodulatory role for leptin in submucosal neurons, where it inhibited the stimulatory effects of IL-6. Functionally, this translated to suppression of IL-6-evoked potentiation of veratridine-induced secretory currents. Leptin also attenuated IL-6-induced colonic contractions, although it had little direct effect on myenteric neurons. Calcium responses evoked by IBS plasma in both myenteric and submucosal neurons were also suppressed by leptin, possibly through interactions with IL-6, which is elevated in IBS plasma. As leptin has the capacity to ameliorate the neurostimulatory effects of soluble mediators in IBS plasma and modulated IL-6-evoked changes in bowel function, leptin may have a role in immune-mediated bowel dysfunc

Topics: Adolescent; Adult; Aged; Animals; Colon; Cytokines; Gastrointestinal Motility; Humans; Interleukin-6; Irritable Bowel Syndrome; Leptin; Male; Middle Aged; Neurons; Rats; Rats, Sprague-Dawley; Young Adult

Fatigue is an important determinant of altered quality of life in patients affected by chronic hepatitis C or the irritable bowel syndrome (IBS).. In this study, we aimed at determining the contributory role of plasma levels of leptin and carnitine on fatigue in chronic hepatitis C and IBS.. We enrolled 81 patients with chronic hepatitis C, 42 with IBS and 44 healthy subjects. Fatigue was evaluated using the Fatigue Impact Scale questionnaire. Body composition was assessed through impedance analysis. Plasma carnitine and leptin were measured.. Fatigue scores were significantly more elevated in patients with chronic hepatitis C and IBS than in healthy subjects. Patients with chronic hepatitis C but not IBS, had significant lower plasma levels of total and free carnitine adjusted for fat mass compared with healthy subjects. In patients with chronic hepatitis C and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine. Levels of free carnitine were significantly and independently associated with the severity of fatigue in patients with chronic hepatitis C [OR=2.019, P=0.02, CI 95% (1.01-1.23)].. In patients with chronic hepatitis C, the severity of fatigue is associated with a low level of carnitine, suggesting that an oral supplementation may be effective to relieve fatigue in chronic hepatitis C. The underlying mechanism of fatigue in IBS does not seem to involve carnitine.

Topics: Adult; Aged; Aged, 80 and over; Body Composition; Carnitine; Case-Control Studies; Electric Impedance; Fatigue; Female; Hepatitis C, Chronic; Humans; Irritable Bowel Syndrome; Leptin; Male; Middle Aged; Quality of Life; Surveys and Questionnaires

This study was undertaken to investigate the relationship between serum leptin levels and the development irritable bowel syndrome (IBS).. Stress has been known as an important causative factor in IBS. Various studies have indicated the relationship between serum leptin levels and stress levels. So searching the relationship between the production and level of this hormone and development of IBS may help to understand the pathophysiology of the disease.. This was a case-control study. Eighty IBS patient and 80 controls were recruited. All participants were asked to fill in a questionnaire included demographic information and medical history and also a stress questionnaire. Serum leptin level was measured by enzyme-linked immunosorbent assay method. Chi-square, Student t test, Pearson correlation and logistic regression were used for investigating the relationships between variables.. Mean serum leptin levels were 7.41 and 19.33 ng/mL in IBS and control groups, respectively (P<0.001). Participants in IBS group had significantly higher stress levels than controls (P<0.001). Multivariate logistic regression analysis showed that adjusted odds ratios (ORs) for serum leptin level (OR: 0.9; 95% confidence interval: 0.85-0.94) and stress level (OR: 1.15; 95% confidence interval: 1.09-1.23) were nearly the same as crude ones.. This study indicated the relationship between leptin and IBS for the first time. Our results show that serum leptin level is significantly lower in IBS group than controls and this relationship is independent of other variables such as stress levels, body mass index, etc. This may help in better understanding of the pathogenesis of IBS and consequently lead to the development of more effective treatments.

Topics: Adult; Biomarkers; Case-Control Studies; Chi-Square Distribution; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Humans; Irritable Bowel Syndrome; Leptin; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Stress, Psychological; Young Adult

Fatigue has received little attention in the irritable bowel syndrome. Emerging evidence exists that leptin may be involved in the pathogenesis of fatigue in several conditions. We aimed to evaluate the occurrence of fatigue and its characteristics in irritable bowel syndrome and to analyze the relationship between fatigue and leptin.. We enrolled 51 consecutive irritable bowel syndrome patients and 22 healthy controls without fatigue. None of them were depressed. The Fatigue Impact Scale was used to evaluate fatigue.. In all, 62.7% of irritable bowel syndrome patients verbally expressed fatigue and rated more than 4 on the visual analog scale. The total score of fatigue was significantly higher in irritable bowel syndrome than in controls. In irritable bowel syndrome patients, but not in controls, a significant association was found between the total score of fatigue and leptin and this association was more pronounced in 32 irritable bowel syndrome patients who verbally expressed fatigue (r=0.60; P=0.0003). In irritable bowel syndrome, leptin correlated with fatigue independently from age, sex, fat mass and body mass index.. Our study shows that fatigue occurs in 62.7% of irritable bowel syndrome patients when systematically asked for. Fatigue influences all three domains of the Fatigue Impact Scale in irritable bowel syndrome, the most being the physical and the psychosocial domains. Fatigue is associated with circulating leptin levels independently from age, sex, fat mass and body mass index in irritable bowel syndrome. The metabolic sequence involved in the occurrence of fatigue remains to be determined.

Topics: Adult; Aged; Body Composition; Fatigue; Female; Humans; Irritable Bowel Syndrome; Leptin; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Sex Factors