The Relationship between Serum Zonulin Level and Clinical and Laboratory Parameters of Childhood Obesity

Objective: To investigate the relationship between zonulin levels and clinical and laboratory parameters of childhood obesity. Methods: The study included obese children with a body mass index (BMI) >95th percentile and healthy children who were of similar age and gender distribution. Clinical (BMI, waist circumferences, mid-arm circumference, triceps skinfold, percentage of body fat, systolic blood pressure, diastolic blood pressure) and biochemical (glucose, insulin, lipid levels, thyroid function tests, cortisol, zonulin and leptin levels) parameters were measured. Results: A total of 43 obese subjects (23 males, mean age: 11.1±3.1 years) and 37 healthy subjects (18 males, mean age: 11.5±3.5 years) were included in this study. Obese children had significantly higher insulin, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), zonulin and leptin levels than healthy children (p<0.05), while glucose levels were not different (p>0.05). Comparison of the obese children with and without insulin resistance showed no statistically significant differences for zonulin levels (p>0.05). Zonulin levels were found to negatively correlate with HDL-C and positively correlate with leptin levels, after adjusting for age and BMI. Conclusion: To the best of our knowledge, this is the first study investigating the relationship between circulating zonulin level (as a marker of intestinal permeability) and insulin resistance and leptin (as markers of metabolic disturbances associated with obesity) in childhood obesity. The results showed that zonulin was significantly higher in obese children when compared to healthy children, a finding indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances.

[1]  L. Pacifico,et al.  Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease. , 2014, World journal of gastroenterology.

[2]  F. Yue,et al.  Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients. , 2014, Diabetes research and clinical practice.

[3]  Alan D. Lopez,et al.  Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2014, The Lancet.

[4]  A. Abacı,et al.  The relation of leptin and soluble leptin receptor levels with metabolic and clinical parameters in obese and healthy children , 2014, Peptides.

[5]  J. Chudek,et al.  Gut Microbiota, Microinflammation, Metabolic Profile, and Zonulin Concentration in Obese and Normal Weight Subjects , 2013, International journal of endocrinology.

[6]  E. Andrès,et al.  Metabolic inflammation: Connecting obesity and insulin resistance , 2013, Annals of medicine.

[7]  J. Moreno-Navarrete,et al.  Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance , 2012, PloS one.

[8]  B. Fagerberg,et al.  Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women , 2011, Obesity.

[9]  R. Speich,et al.  MicroRNA-18a Enhances the Interleukin-6-mediated Production of the Acute-phase Proteins Fibrinogen and Haptoglobin in Human Hepatocytes* , 2011, The Journal of Biological Chemistry.

[10]  A. Fasano.  Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. , 2011, Physiological reviews.

[11]  P. Scherer,et al.  Adipokines as novel biomarkers and regulators of the metabolic syndrome , 2010, Annals of the New York Academy of Sciences.

[12]  J. Rutledge,et al.  Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. , 2010, American journal of physiology. Gastrointestinal and liver physiology.

[13]  A. Fasano.  Surprises from celiac disease. , 2009, Scientific American.

[14]  T. van de Wiele,et al.  Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability , 2009, Gut.

[15]  Sefik Alkan,et al.  Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. , 2008, Gastroenterology.

[16]  R. Bibiloni,et al.  Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice , 2008, Diabetes.

[17]  C. Wijmenga,et al.  Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitisAn unusual case of ascites , 2007, Gut.

[18]  A. Franzese,et al.  Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy. , 2006, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[19]  F. Bäckhed,et al.  Host-Bacterial Mutualism in the Human Intestine , 2005, Science.

[20]  S. Haffner,et al.  Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study. , 2005, Metabolism: clinical and experimental.

[21]  S. Simpson.  Of Mice . . . , 2004, Science.

[22]  B. Rosner,et al.  Blood pressure nomograms for children and adolescents, by height, sex, and age, in the United States , 1993, Pediatric Nephrology.

[23]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[24]  G. Coppa,et al.  Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. , 2002, Gastroenterology.

[25]  Shumei S. Guo,et al.  2000 CDC Growth Charts for the United States: methods and development. , 2002, Vital and health statistics. Series 11, Data from the National Health Survey.

[26]  Shumei S. Guo,et al.  CDC GROWTH CHARTS FOR THE UNITED STATES: METHODS AND DEVELOPMENT 2000 , 2002 .

[27]  A. Fasano,et al.  Human zonulin, a potential modulator of intestinal tight junctions. , 2000, Journal of cell science.

[28]  A. Fasano,et al.  Regulation of Intercellular Tight Junctions by Zonula Occludens Toxin and Its Eukaryotic Analogue Zonulin , 2000, Annals of the New York Academy of Sciences.

[29]  J. Halaas,et al.  Leptin and the regulation of body weight in mammals , 1998, Nature.

[30]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[31]  R. Ferraris,et al.  Intestinal nutrient transport in genetically obese mice. , 1995, The American journal of clinical nutrition.

[32]  R. Ferraris,et al.  Dietary Carbohydrate Enhances Intestinal Sugar Transport in Diabetic Mice , 1993, Diabetes.

[33]  J. Tanner,et al.  Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. , 1976, Archives of disease in childhood.