Abstract

Background: Zonulin is the endogenous protein known to control the permeability of intestinal tight junction reversibly. Zonulin is actively engaged in intestinal innate immunity and is over-expressed in autoimmune diseases where tight junction of intestine plays a pivotal role, such as celiac disease, malabsorption disorder, and type 1 diabetes. Waist-Height ratio was well known as one of indices of obesity and also Waist-Hip ratio was known of abdominal obesity. We investigated that the associations among Waist-Height, Waist-Height ratio, and the level of Zonulin by assessing obesity-related biomarkers, such as liver enzymes, lipid profiles, and insulin resistance, in a population of adolescents. Methods: The study included 198 adolescents aged 12-18 years; 92 were overweight/obese and 106 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), BMI z-score, Waist-Height, Waist-Hip ratio, blood pressure, liver enzyme levels, lipid profiles, and insulin sensitivity. Serum Zonulin levels were measured using an enzyme-linked immunosorbent assay. Results: The mean age of the participants was 15.2±2.5 years. Circulating serum Zonulin levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (P=0.042). Zonulin levels were significantly and positively associated with BMI, BMI z-score, alanine aminotransferase levels, triglyceride, fasting insulin, and insulin resistance as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, alanine aminotransferase (P<0.0001), triglyceride (P<0.0001), and HOMA-IR (P=0.001) contributed independently to circulating Zonulin levels after controlling for the effect of BMI z-score. Zonulin levels were more strongly associated with Waist-Hip ratio rather than Waist-Height ratio. Conclusions: Zonulin was associated with indices of obesity. Waist-Hip ratio was more strongly associated with levels of Zonulin. The positive correlation between these parameters suggests putative pathophysiological mechanism linking Zonulin to metabolic dysfunction in adolescents.

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