REGRESSION OF CHOLESTEROL ACCUMULATION IN RATS THROUGH ALTERATION OF FECAL BILE ACID EXCRETION BY DIETARY FIBER

JAMES NEAL THOMAS, Purdue University

Abstract

These studies were designed to better understand the role of dietary fiber in the regression of accumulated lipids in the rat. In the first experiment, rats were fed diets containing cholesterol (1%) for 4 weeks, and then switched to either a Basal (B) or Basal plus pectin (BP) diet for 8 additional weeks. Fecal samples were collected each week and analyzed for acidic and neutral steroids. Animals from both groups were sacrificed every two weeks beginning at week 4 and liver and serum cholesterol and triglycerides were determined. In the second experiment rats were fed a commercial laboratory ration and injected with a solution containing either 2.0 or 4.0 (mu)Ci of {4 - ('14)C}cholesterol and 5.0 or 10.0 (mu)Ci of {5 - ('3)H(N)}mevalonolactone. Two or three rats were sacrificed every 12 hours and the radioactivity in their liver and feces quantitated. The third experiment was designed similar to the first, except 3 groups of rats were fed diets containing either cellulose (BC), lignin (BL) or pectin (BP) after being fed a cholesterol containing diet for 4 weeks. Pectin fed animals in the first experiment excreted much higher levels of bile acids but lower levels of neutral steroids than control groups. Serum cholesterol in BP fed animals was significantly lower on some weeks than B fed animals, but both B and BP fed animals were extremely efficient in excreting excess liver cholesterol. The second experiment produced important data concerning the dose size of injected radioactive labels and the optimum time of their collection from tissues. It was found that rats consuming a commercial laboratory ration had 85 to 87 percent of total liver radioactivity in the free cholesterol pool. The specific activities of ('3)H-labeled bile acids were found to be higher than those of ('3)H-labeled neutral steroids but the specific activities of ('14)C-labeled bile acids were lower than those of ('14)C-labeled neutral steroids. Animals fed pectin in the third experiment excreted more bile acids and less neutral steroids than animals fed cellulose or lignin containing diets. The majority of bile acids excreted by BP fed animals in the regression period after 3 days were CA and DCA whereas CDCA and its metabolites composed the largest percentage of bile acids of BL and BC fed animals. The specific activities of ('3)H-labeled bile acids were highest in BP fed animals and higher in all groups than the specific activities of ('3)H-labeled neutral steroids. Regression of accumulated liver cholesterol was similar in all groups, but somewhat more efficient in BP and BL fed animals. The percentage of total radioactivity in the liver contained in the esterified fraction decreased with time, and BP fed animals were more effective than BC or BL fed animals in causing this decrease. Pectin containing diets were slightly more effective than other diets in causing the regression of accumulated lipids, although differences between groups were not as great as expected. The lack of expected differences may be the result of the rats natural ability to excrete excess cholesterol through increased synthesis and excretion of chenodeoxycholic acid and its metabolites. Pectin may act in addition to this natural mechanism by causing an increase in cholic acid synthesis and excretion. This mechanism along with the rats natural mechanism for increasing bile acid synthesis are discussed with special attention given to the precursor sources for bile acids.

Degree

Ph.D.

Subject Area

Nutrition

COinS