Rechallenge Following an Early Life Exposure to a High-Cholesterol Diet Enhances Diet-Associated Alterations in Intestinal Permeability

Abstract

This study was undertaken to test the hypothesis that the intestinal transport response to a high-cholesterol (2%) diet (HCD) is influenced by prior exposure to HCD at an earlier age. Uptake was assessed using an in vitro technique, and rabbits were fed one of four dietary regimens: chow for 20 weeks, chow for 14 weeks followed by HCD for 6 weeks, chow for 2 weeks followed by 4 weeks HCD followed by chow for 14 weeks, or 2 weeks chow followed by 4 weeks HCD followed by 8 weeks chow and then 6 further weeks with HCD. The passive jejunal uptake of octanoic, lauric, cholic, and taurocholic acids was greater in animals previously exposed at an earlier age to HCD, as compared with those first exposed to HCD at a later age. Furthermore, the effect of HCD on the passive permeability properties of the intestine lasted for as long as 14 weeks after the animals were switched from HCD back to chow. These alterations in permeability properties occurred in the absence of changes in the intestinal mucosal surface area and were not explained by differences in the rabbits' body weight gain, food consumption, or mucosal surface area of the jejunum or ileum. Thus, (a) early changes in animals' dietary content of cholesterol may have prolonged effects on intestinal transport function, and (b) this early feeding experience with cholesterol may alter the adaptive pattern of the intestine when animals are exposed to a dietary cholesterol challenge at a later age.