Long-term cholesterol feeding stimulates increased bile phospholipids and gallbladder prostanoid synthesis

The effect of long-term cholesterol feeding on male rabbit gallbladder prostanoid synthesis and bile phospholipid and bile acid levels was examined. In rabbits fed a 2% cholesterol diet for 2, 5, 7, 9, 12, 15, 18, and 21 weeks, serum cholesterol levels increased 12-fold or higher (68-fold at 21 weeks) when compared to the control levels. Total prostanoid synthesis was significantly increased at 7 weeks or more of cholesterol feeding with 6-keto PGF1 alpha (PGI2 metabolite) and PGE2 as the major products. By 21 weeks of cholesterol feeding, 6-keto PGF1 alpha and PGE2 levels were increased 15-fold and 11-fold higher, respectively, compared to the control. Total bile phospholipid levels were significantly increased at 12 weeks or more of cholesterol feeding, and total bile acids significantly increased only from 5 through 12 weeks of cholesterol feeding. These data show that long-term feeding male rabbits with a 2% cholesterol diet increased endogenous gallbladder prostanoid synthesis, which was associated with an increase in bile phospholipid levels. Increased rabbit gallbladder bile phospholipids may represent a compensation of the animal for toxic levels of tissue and bile cholesterol. Increased phospholipid levels in the bile or tissue could serve as a source of increased availability of arachidonic acid leading to a nonspecific increase in gallbladder prostanoid synthesis.