leptin and Celiac-Disease

Reduced bone mass and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Undoubtedly, genetics play an important role, but other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in inflammatory bowel disease (IBD) and other lifestyle factors, such as smoking or being sedentary, may contribute to reduced bone mass. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD and probably also in coeliac disease are also known to enhance bone resorption. The discovery of the role of the receptor to activated NFkappaB (RANK) interaction with its ligand RANKL in orchestrating the balance between bone resorption and formation may link mucosal and systemic inflammation with bone remodelling, since RANK-RANKL are also involved in lymphopoiesis and T-cell apoptosis. Low circulating leptin in response to weight loss in any gastrointestinal disease may be an important factor in reducing bone mass. This report will summarize current concepts regarding gastrointestinal diseases (primarily IBD, coeliac disease and postgastrectomy states) and low bone mass and fracture.

Topics: Bone and Bones; Bone Density; Celiac Disease; Diagnosis, Differential; Gastrectomy; Gastrointestinal Diseases; Humans; Inflammatory Bowel Diseases; Leptin; Nutritional Status; Osteomalacia; Osteoporosis; Risk Factors; Vitamin D

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

Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.. The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease.. After accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.. Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013).

Topics: Biomarkers; Case-Control Studies; Celiac Disease; Cell Proliferation; Child Development; Child, Preschool; Creatinine; DNA Methylation; Epigenome; Female; Ferritins; Genomics; Growth Disorders; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Intestinal Diseases; Intestinal Mucosa; Leptin; Lipid Metabolism; Lymphocyte Activation; Lymphocytes; Male; Malnutrition; Oxidative Stress; Pakistan; Transcriptome

A gluten-free diet (GFD) has been reported to negatively impact the quality of life (QoL) of coeliac disease (CD) patients. The gut-brain axis hormones ghrelin and leptin, with the brain-derived neurotrophic factor (BDNF), may affect QoL of CD patients undergoing GFD. Our aims were to evaluate whether: (a) the circulating concentrations of leptin, ghrelin and BDNF in CD patients were different from those in healthy subjects; (b) GFD might induce changes in their levels; (c) BDNF Val66Met polymorphism variability might affect BDNF levels; and (d) serum BDNF levels were related to dietary docosahexaenoic acid (DHA) as a neurotrophin modulator.. Nineteen adult coeliac patients and 21 healthy controls were included. A QoL questionnaire was administered, and serum concentrations of ghrelin, leptin, BDNF and red blood cell membrane DHA levels were determined at the enrolment and after 1 year of GFD. BDNF Val66Met polymorphism was analysed.. Results from the questionnaire indicated a decline in QoL after GFD. Ghrelin and leptin levels were not significantly different between groups. BDNF levels were significantly (p = 0.0213) lower in patients after GFD (22.0 ± 2.4 ng/ml) compared to controls (31.2 ± 2.2 ng/ml) and patients at diagnosis (25.0 ± 2.5 ng/ml). BDNF levels correlated with DHA levels (p = 0.008, r = 0.341) and the questionnaire total score (p = 0.041, r = 0.334).. Ghrelin and leptin seem to not be associated with changes in QoL of patients undergoing dietetic treatment. In contrast, a link between BDNF reduction and the vulnerability of CD patients to psychological distress could be proposed, with DHA representing a possible intermediate.

Topics: Adult; Alleles; Amino Acid Substitution; Brain-Derived Neurotrophic Factor; Case-Control Studies; Celiac Disease; Diarrhea; Diet, Gluten-Free; Docosahexaenoic Acids; Erythrocyte Membrane; Female; Follow-Up Studies; Gene Frequency; Genetic Association Studies; Ghrelin; Heterozygote; Humans; Italy; Leptin; Male; Polymorphism, Single Nucleotide; Prospective Studies; Quality of Life; Stress, Psychological

The roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence).. Prepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD).. Insulin levels in prepubertal (9.01±4.43 μIU/mL), pubertal (10.3±3.62 μIU/mL), and adolescent (10.8±4.73 μIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 μIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2.. Adherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia.

Topics: Adiponectin; Adolescent; Celiac Disease; Child; Child, Preschool; Diet, Gluten-Free; Female; Ghrelin; Humans; Insulin; Leptin; Lipocalin-2; Male; Patient Compliance; Peptide Hormones; Receptors, Leptin

Previous research indicated that coeliac disease (CD) is associated with type 1 diabetes mellitus (T1DM). However, the gut-brain axis peptide hormones secretion has not been evaluated so far in patients with CD prior to treatment initiation or under treatment, irrespective of patients having concomitant T1DM or not. The aim of the study was therefore to evaluate these gut hormones at the preprandial levels of patients with CD before and under treatment.. Of forty-seven CD children, 12 untreated (UCD), 22 treated with gluten-free diet (TCD) and 13 treated CD with coexisting T1DM (DCD), and 18 healthy controls (HC) were enrolled. Preprandial glucagon-like-peptide-1 (GLP-1), glucose-dependent-insulinotropic-polypeptide (GIP), active amylin, acylated ghrelin (AG), leptin, pancreatic polypeptide (PP) and peptide-tyrosine-tyrosine (PYY) were determined with hormone-map-array technology.. We found in patients with CD compared with HC that the concentration of (i) GLP-1 was reduced remarkably in all patients with CD (P = 0.008), (ii) GIP was lower in patients with UCD (P = 0.008), (iii) amylin was remarkably reduced (P < 0.01) in all patients with CD, (iv) AG was significantly decreased in patients with DCD (P < 0.01), while (v) leptin, PP and PYY were not significantly different. GIP, GLP-1 and amylin levels correlated positively with insulin concentrations (P < 0.001, P = 0.004 and P < 0.01, respectively) in all patients. Amylin and GIP levels were strongly associated with triglycerides concentrations (P < 0.001, for both peptides) in children with CD.. Our study revealed a different secretion pattern of gut-brain axis hormones in children with CD compared with HC. The alterations in the axis were more pronounced in children with both CD and T1DM.

Topics: Adolescent; Case-Control Studies; Celiac Disease; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diet, Gluten-Free; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Incretins; Islet Amyloid Polypeptide; Leptin; Male; Pancreatic Polypeptide; Peptide YY

The main aim of this study was to assess the nutritional status of children with newly diagnosed Coeliac disease (CD)with comparison to matched controls. A further aim was to assess relationships between presentation patterns and nutrition in childhood CD.. The nutritional status of newly diagnosed CD was assessed by anthropometry, Bioelectrical Impedance and serum leptin levels, and contrasted to age and gender matched controls.. Twenty-five children with CD (mean age of 8.2 +/- 4.5 years) and 25 control children (mean age 8.1 +/- 4.4.) were enrolled. Thirteen (52%) children with CD had gastrointestinal symptoms with 14 having a family history of CD. At presentation 8.7% were wasted, 4.2% were stunted and 20.8% overweight, although none were obese. Mean height and weight for age, other nutritional parameters and serum leptin did not differ between the groups. Serum leptin correlated with BMI in both groups.. Children with CD more commonly present with atypical symptoms than with classical features. Variations in nutrition (under to overnutrition) may be seen at diagnosis, without relationship to the presence of symptoms. Leptin levels were not altered specifically in the setting of CD. Nutritional assessment remains important in the assessment and management of CD in children.

Topics: Adolescent; Anthropometry; Case-Control Studies; Celiac Disease; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Electric Impedance; Female; Humans; Infant; Leptin; Male; Nutrition Assessment; Nutritional Status

Coeliac disease, daily more frequently diagnosed in our population, involves many organs also in oligosymptomatic patients and with an adequate nutritional regime. Possible endocrine implications include failure to thrive, pubertal delay and reproduction diseases due to deregulation of GH, FSH and LH secretion. Leptin, an adipose tissue hormone, can be decreased as well and its deficiency could be related to growth and puberty anomalies. We studied 14 asymptomatic coeliac patients in peripubertal age (7.5-13.8 years) and tested their leptin levels in order to correlate them with endocrine and anthropometric data. Before the diet was started leptinaemia (M+/-DS) was: 4.94+/-5.53 ng/ml. In 10/14 patients (71%) leptinaemia was

Topics: Adolescent; Body Mass Index; Celiac Disease; Child; Female; Follicle Stimulating Hormone; Follow-Up Studies; Glutens; Humans; Leptin; Luteinizing Hormone; Male; Puberty

Celiac disease (CD) is characterized by malabsorption, weight loss and increased energy expenditure. The aim of this study was to investigate the relationship between circulating ghrelin and leptin, which are produced at gastrointestinal level and are involved in energy balance regulation, and changes in body composition and energy metabolism in CD patients before and after gluten-free diet (GFD)-induced restoration of the intestinal mucosa.. Body composition (by dual-energy X-ray absorptiometry), resting metabolic rate and substrate oxidation rates (by indirect calorimetry) were assessed in 18 adult women with the classic form of CD (age 31.4 +/- 7.8 years, body mass index (BMI) 20.6 +/- 2.1 kg/m2) before and at least 2 years after GFD treatment and in 22 age-matched healthy women (age 33.1 +/- 7.2 years, BMI 22.9 +/- 2.1 kg/m2). Plasma leptin and ghrelin concentrations were assessed by the ELISA and RIA procedures, respectively.. Fat-free mass was reduced before and after GFD compared to control subjects (p < 0.01), while fat mass increased after treatment (p < 0.01). Plasma leptin concentration was similar between groups and correlated only with BMI (r = 0.84; p < 0.0001) and percentage body fat (r = 0.86; p < 0.0001). Circulating ghrelin levels (pg/ml) were similar between untreated patients and control subjects, but decreased after GFD treatment (untreated CD: 282.6 +/- 55.5 versus treated 109.2 +/- 49.9; p < 0.0001 and versus control subjects 262.2 +/- 30.0; p < 0.0001) and were negatively correlated with BMI in CD patients (r = -0.32; p < 0.01).. The low plasma ghrelin concentration found in CD patients after GFD treatment could only be partially explained by the slight increase in body-weight and fat mass. Further studies are needed to better ascertain the role played by an incomplete functional or quantitative recovery of ghrelin-producing cells in CD.

Topics: Adult; Basal Metabolism; Body Composition; Celiac Disease; Female; Ghrelin; Glutens; Humans; Leptin; Peptide Hormones

Patients with coeliac disease (CD) present anorexia and malnutrition. Leptin is a significant anorexigenic factor, with a close relationship to the body mass index. The aims of this study were to asses serum leptin levels in CD and their possible influence on appetite, as well as to compare and relate leptin with tumor necrosis factor (TNF) activity, which has similar functions.. Leptin and TNF receptor-1 (TNFr-1) were measured by enzyme-linked immunosorbent assay. Sixty-five serum samples from patients with CD (28 boys and 37 girls) were analyzed. In all patients, small bowel biopsy and anti-endomysium determination were performed simultaneously. Twenty-nine patients presented active CD and 36 were in remission.. Leptin concentrations were reduced in active CD (p = 0.002). In patients in remission, leptin was related to the body mass index (p = 0.001), but this correlation was not found during the active phase of the disease. Contrary to normal differences between sexes, in active CD leptin levels were similar in boys and girls. TNFr-1 was found in all serum samples and levels were statistically higher in patients with active CD (p = 0.0003), suggesting that the TNF system is activated in this disease.. Leptin concentrations were reduced in active CD, but we did not find the usual positive correlation with body mass index and higher concentrations in girls. These results suggest that leptin does not contribute to anorexia and failure to thrive in patients with CD; in contrast, the TNF system might be involved.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Female; Humans; Infant; Leptin; Male; Tumor Necrosis Factor-alpha