| Summary: | Interindividual and interstrain variations in cholesterol absorptionefficiency occur in humans and animals. We investigated physiological biliaryand small intestinal factors that might determine variations in cholesterolabsorption efficiency among inbred mouse strains. We found that there weresignificant differences in cholesterol absorption efficiency measured by plasma,fecal, and lymphatic methods: <25% in AKR/J, C3H/J, and A/J strains;25–30% in SJL/J, DBA/2J, BALB/cJ, SWR/J, and SM/J strains; and31–40% in C57L/J, C57BL/6J, FVB/J, and 129/SvJ strains. In(AKR×C57L)F1 mice, the cholesterol absorption efficiency(31 ± 6%) mimicked that of the C57L parent (37 ± 5%) and wassignificantly higher than in AKR mice (24 ± 4%). Although biliary bilesalt compositions and small intestinal transit times were similar, C57L micedisplayed significantly greater bile salt secretion rates and pool sizes thanAKR mice. In examining lymphatic cholesterol transport in the setting of achronic biliary fistula, C57L mice displayed significantly higher cholesterolabsorption rates compared with AKR mice. Because biliary and intestinal transitfactors were accounted for, we conclude that genetic variations at theenterocyte level determine differences in murine cholesterol absorptionefficiency, with high cholesterol absorption likely to be a dominant trait. Thisstudy provides baseline information for identifying candidate genes thatregulate intestinal cholesterol absorption at the cellular level.—Wang, D. Q-H., B. Paigen, and M. C. Carey. Genetic factors atthe enterocyte level account for variations in intestinal cholesterol absorptionefficiency among inbred strains of mice.
|
|---|
