Abstract
In the present study, we investigated whether intestinal sterol efflux transporters Abcg5 and Abcg8 play a major role in determining variations in cholesterol (Ch) absorption efficiency, and we compared the physiological functions of the duodenal, jejunal, and ileal Abcg5 and Abcg8 on the absorption of Ch and sitostanol in inbred mice challenged with various amounts of Ch, sitostanol, hydrophilic, or hydrophobic bile acids. We found that Abcg5 and Abcg8 in the jejunum and ileum, but not in the duodenum, were main factors in determining, in part, variations in Ch absorption efficiency. The jejunal and ileal Abcg5 and Abcg8 played a major regulatory role in response to high dietary cholesterol and were more sensitive in the regulation of Ch absorption when compared with sitostanol absorption. These results, combined with different sterol uptake rates, suggest that the absorption efficiency of Ch and sitostanol is determined by the net results between influx and efflux of intraluminal Ch and sitostanol molecules crossing the apical membrane of the enterocyte. Hydrophilic and hydrophobic bile acids influenced Ch absorption through mediating Ch solubilization and its physical-chemical state within the small intestinal lumen. We conclude that Ch absorption is mainly regulated by the jejunal and ileal Abcg5 and Abcg8 in mice.
Highlights
In the present study, we investigated whether intestinal sterol efflux transporters Abcg5 and Abcg8 play a major role in determining variations in cholesterol (Ch) absorption efficiency, and we compared the physiological functions of the duodenal, jejunal, and ileal Abcg5 and Abcg8 on the absorption of Ch and sitostanol in inbred mice challenged with various amounts of Ch, sitostanol, hydrophilic, or hydrophobic bile acids
We i) studied whether the intestinal sterol efflux transporters Abcg5 and Abcg8 play a major role in determining variations in Ch absorption efficiency in inbred mice; ii) compared the physiological functions of the duodenal, jejunal, and ileal Abcg5 and Abcg8 on the absorption of Ch and sitostanol; and iii) investigated whether both transporters influence intestinal Ch absorption in mice challenged with various amounts of high dietary Ch with or without sitostanol, as well as hydrophilic or hydrophobic bile acids
Mice, AKR mice showed a significantly higher fecal total neutral steroid excretion (Table 2). These data suggest that in response to high dietary Ch, the jejunal and ileal sterol transporters Abcg5 and Abcg8 may efflux more Ch from the enterocyte back into the lumen and reduce its fractional absorption in AKR mice than in C57L mice. This kind of response was not observed in both strains of mice fed sitostanol until its concentration in the diet was increased to 2%, suggesting that there may be a selective regulatory mechanism between Ch and sitostanol absorption, and the intestinal Abcg5 and Abcg8 may be more sensitive in the regulation of Ch absorption compared with sitostanol absorption
Summary
We investigated whether intestinal sterol efflux transporters Abcg and Abcg play a major role in determining variations in cholesterol (Ch) absorption efficiency, and we compared the physiological functions of the duodenal, jejunal, and ileal Abcg and Abcg on the absorption of Ch and sitostanol in inbred mice challenged with various amounts of Ch, sitostanol, hydrophilic, or hydrophobic bile acids. We i) studied whether the intestinal sterol efflux transporters Abcg and Abcg play a major role in determining variations in Ch absorption efficiency in inbred mice; ii) compared the physiological functions of the duodenal, jejunal, and ileal Abcg and Abcg on the absorption of Ch and sitostanol; and iii) investigated whether both transporters influence intestinal Ch absorption in mice challenged with various amounts of high dietary Ch with or without sitostanol, as well as hydrophilic or hydrophobic bile acids
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