Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice.

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.