Genetic factors at the enterocyte level account for variations in intestinal cholesterol absorption efficiency among inbred strains of mice

Interindividual and interstrain variations in cholesterol absorption effici ency occur in humans and animals. We investigated physiological biliary and small intestinal factors that might determine variations in cholesterol ab sorption efficiency among inbred mouse strains. We found that there were si gnificant differences in cholesterol absorption efficiency measured by plas ma, 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; and 31-40% in C57L /J, C57BL/6J, FVB/J, and 129/SvJ strains. In (AKR x C57L)F-1 mice, the chol esterol absorption efficiency (31 +/- 6%) mimicked that of the C57L parent (37 +/- 5%) and was significantly higher than in AKR mice (24 +/- 4%). Alth ough biliary bile salt compositions and small intestinal transit times were similar, C57L mice displayed significantly greater bile salt secretion rat es and pool sizes than AKR mice. In examining lymphatic cholesterol transpo rt in the setting of a chronic biliary fistula, C57L mice displayed signifi cantly higher cholesterol absorption rates compared with AKR mice. Because biliary and intestinal transit factors were accounted for, we conclude that genetic variations at the enterocyte level determine differences in murine cholesterol absorption efficiency, with high cholesterol absorption likely to be a dominant trait. This study provides baseline information for ident ifying candidate genes that regulate intestinal cholesterol absorption at t he cellular level.