Cholesterol metabolism in lean and obese Zucker rats: effects of portacaval anastomosis.

The effects of portacaval anastomosis (PCA) on cholesterol biodynamics of male adult (fa/fa) Zucker rats and their lean littermates were studied with an isotopic equilibrium method. Animals were fed with a sucrose-rich semi-purified diet. Obese rats were hypercholesterolemic (2.03 +/- 0.14 vs 1.06 +/- 0.7 mg/ml), had a cholesterol-enriched liver (135.3 +/- 14.5 vs 40.0 +/- 2.6 mg/liver) and accumulated cholesterol in body pools. However no difference in the rates of cholesterol absorption, synthesis, fecal elimination or transformation into bile acids distinguished obese from lean Zucker rats. In both lean and obese rats, PCA decreased cholesterolemia by about 28 per cent and liver weight by 40 per cent while the total cholesterol content of the liver was not affected. Input of synthesized cholesterol (internal secretion) was strikingly decreased by the shunt (from 13.2 +/- 0.6 and 12.6 +/- 0.7 mg/day/rat before PCA, to 8.9 +/- 0.8 and 8.6 +/- 1.0 mg/day/rat after PCA) in lean and obese rats respectively. A similar decrease was observed in the cholesterol transformation into bile acids. Since the activity of the gut for cholesterol synthesis, as shown by the fecal external secretion (cholesterol synthesized by the gut and directly eliminated in the gut and feces) was probably not modified, the reduction of internal secretion induced by PCA resulted from decreased hepatic cholesterogenesis. It is suggested that this decrease may be one of the factors involved in the lowering effect of PCA on plasma cholesterol level.