Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.
Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Girona, Spain.
José María
JM
Moreno-Navarrete
Mònica
M
Sabater
Francisco
F
Ortega
Wifredo
W
Ricart
José Manuel
JM
Fernández-Real
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D002772:Cholera Toxin / Q000097:blood*; D005951:Glucose Tolerance Test; D006242:Haptoglobins; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D010539:Permeability; D011498:Protein Precursors; D014527:Uric Acid / Q000097:blood; D049629:Waist-Hip Ratio
D001786:Blood Glucose; D006242:Haptoglobins; D015850:Interleukin-6; D011498:Protein Precursors; C408043:zonulin; D014527:Uric Acid; D002772:Cholera Toxin