Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats

Four germfree rats were fed a basal diet containing 0.004% cholesterol and four germfree rats received the same diet supplemented with 0.4% cholesterol for 2 weeks. Cholesterol synthesis was studied by assaying the HMG CoA reductase activity in the liver microsomal fraction. Cholesterol feeding decreased the HMG CoA reductase activity from 28.5 ± 6.6 (mean ± SEM) to 9.1 ± 0.7 pmol/mg protein per min. In another experiment four germfree rats received the basal diet and four germfree rats the cholesterol-enriched diet. After 6 weeks feces were collected in two 4-day pools for analysis of bile acids. The main fecal bile acids were cholic acid and β-muricholic acid (a metabolite of chenodeoxycholic acid), comprising more than 95% of total bile acids. Cholic acid was increased from 3.9 ± 0.2 to 9.9 ± 1.2 mg/kg body weight per day and β-muricholic acid from 6.6 ± 0.5 to 21.8 ± 3.1 mg/kg body weight per day. The percentage of cholic acid decreased from 37.1 ± 1.1 to 31.2 ± 1.0%. In conclusion, germfree rats like conventional rats have the ability to compensate for an increased input of dietary cholesterol by inhibition of cholesterol synthesis and stimulation of bile acid synthesis. The synthesis of chenodeoxycholic acid (implied from the fecal excretion of β-muricholic acid) is stimulated to a greater extent than that of cholic acid.