IAP represents the first layer of the intestinal barrier and detoxifies bacterial endotoxin LPS in the gut lumen. Reduced levels of IAP are associated with diabetes and heart disease. We developed intestine specific IAP transgenic mice (IAPTg) and demonstrated attenuation of WD-induced intestinal barrier dysfunction and glucose intolerance. In this study, we crossed the IAPTg mice into LDLR-/- background to examine the effects on atherosclerosis. Panel A shows significant reduction in plasma total cholesterol (TC) and triglyceride (TG) in LDLR-/-IAPTg mice. There was a small but statistically non-significant improvement in glucose tolerance (Panel B). Enface analyses (Panel C) showed significant reduction in arch and total aortic lesions (Panel D). Expression of IAP was observed along the entire length of the GI tract including colon (Panel E). Expression of Muc-2, major protein of the mucin or the second layer of the intestinal barrier was enhanced in colon of IAPTg mice. Increased expression of GLP-1 was also noted in the ileum of IAPTg mice. These data suggest that in addition to limiting LPS-mediated intestinal inflammation, IAP also improves intestinal barrier function by increasing Muc-2 expression and IAP-modulated increase in ileal GLP-1 expression may contribute to the improved glucose tolerance.
S.S. Ghosh: None. J. Wang: None. P.J. Yannie: None. Y.K. Sandhu: None. S. Ghosh: None.
American Diabetes Association (1-16-IBS-105 to S.G.)