Intestinal Absorption Of Biliary Cholesterol Research Articles

Physical chemistry of intestinal absorption of biliary cholesterol in mice†

Although many putative sterol transporters influencing cholesterol absorption and physical-chemical factors affecting dietary cholesterol absorption have been extensively investigated, it is still unclear how biliary cholesterol contributes to the regulation of intestinal cholesterol absorption. We studied whether the gallbladder can modulate the microaggregates of cholesterol carriers, which may in turn influence the intestinal absorption of biliary cholesterol. Supersaturated, crystallized, or micellar model biles were delivered via a duodenal catheter to conscious, freely moving C57L mice daily for 2 days. Intestinal uptake and absorption of biliary cholesterol and its fecal excretion, as well as expression levels of intestinal sterol transporters, were analyzed. Cholesterol uptake and absorption by the enterocyte were dramatically reduced in mice treated with crystallized biles compared with supersaturated biles. This correlated with the higher cumulative radioactivity of cholesterol recovered in the feces at 24 hours. Such findings were absent with the added reference compound sitostanol. After removing cholesterol crystals from crystallized biles, micellar biles showed essentially identical effects on intestinal absorption but with lower fecal cholesterol excretion compared with the original samples containing crystals. Expression levels of the jejunal Abcg5 (ATP-binding cassette transporter G5) and Abcg8, but not Npc1l1 (Niemann-Pick C1 like 1), were significantly increased by supersaturated biles compared with crystallized biles. Different physical forms of biliary cholesterol dramatically determine intestinal uptake and absorption of cholesterol. Solid plate-like cholesterol monohydrate crystals in bile are probably not absorbed and are totally excreted in feces from the body. The gallbladder may have a role in regulating cholesterol homeostasis by modulating the physical forms of biliary cholesterol.

Biliary Anionic Peptide Fraction and ApoA-I Regulate Intestinal Cholesterol Uptake

Evidence is now in favor of protein-facilitated mechanisms for the intestinal cholesterol absorption. Here we report that the unesterified cholesterol uptake by rat jejunal brush border membrane vesicles (BBMVs) is efficient, saturable, and protein-mediated. The human apolipoproteins biliary anionic peptide factor (APF) and A-I (apoA-I) up-regulate micellar cholesterol uptake in a dose-dependent manner, but for all tested concentrations (0.1–20 μM), the lipid-free APF was more efficient than apoA-I. This uptake stimulation was suppressed after addition of Pabs directed to the external lipid-binding domain of the CLA-1/SR-BI and reduced by Pabs directed to the external loop of CD36. Thus, CLA-1/SR-BI and to a lesser extent CD36 are involved in the regulation of intestinal cholesterol uptake. APF, the main protein bound to biliary lipids, is likely one of their physiological effectors. As APF is an unesterified cholesterol carrier, it could facilitate the intestinal absorption of biliary cholesterol.