Stearic acid (18:0) is unique among the saturated fatty acids commonly found in the food supply because, unlike palmitic, myristic and lauric acid, it does not raise plasma cholesterol when consumed (1-3). Studies in rats (4 -6) and hamsters (7,8) have indicated that dietary 18:0 also reduces liver cholesterol concentration. The hypocholesterolemic effect of dietary 18:0 is related to a reduction in intestinal cholesterol absorption (9 -12) and increased cholesterol excretion from the body (4,7,13). Nevertheless, it is still unclear exactly how 18:0 alters cholesterol absorption.Our present hypothesis is that dietary 18:0 reduces cholesterol absorption by altering hepatic bile acid synthesis and gallbladder bile acid composition. Because intestinal absorption of cholesterol requires secretion of bile acids and formation of mixed micelles, the efficiency of cholesterol solubilization, and therefore absorption, depends in part on the relative hydrophobicity of the bile acids present in bile. Using relative hydrophobicity values established for individual bile acids (14), a "hydrophobicity index" was developed to describe the overall hydrophilic-hydrophobic balance of a bile acid mixture (15). Studies in rats (6) and hamsters (8) have shown that dietary 18:0 alters fecal bile acid composition, suggesting that 18:0 could reduce intestinal cholesterol absorption by decreasing the proportion of hydrophobic bile acids secreted into the small intestine.This work is an extension of a previous study in which we reported significantly reduced cholesterol absorption and increased cholesterol excretion in hamsters fed 18:0-enriched diets (16). A unique aspect of the study design is that hamsters were fed modified NIH-07 open formula diets that differed in only a single fatty acid, i.e., 18:0, palmitic acid (16:0), trans fatty acids (18:1t), oleic acid (18:1c) or linoleic acid (18:2). This design eliminated the confounding variable of multiple fatty acid difference among treatments and allowed us to isolate the metabolic effects of the specific fatty acids.
MATERIALS AND METHODS
Animals and diets. Male Syrian hamsters (ϳ30 d old; CharlesRiver, Wilmington, MA) weighing ϳ70 g were housed individually in polycarbonate cages with sawdust bedding. Hamsters were kept in an environmentally controlled room at 25°C with a 12-h light:dark cycle. They were fed a modified version of the NIH-07 open formula, cereal-based rodent diet (17,18). Each diet provided (g/100 g) 17 total fat, 24 protein, 40 carbohydrate, 4 crude fiber and 0.05 cholesterol. Details of diet formulation and composition are published elsewhere (16). Syrian hamsters were used in this study because of their well documented similarities to human cholesterol and bile acid metabolism (19). All experimental procedures were approved by the Institutional Animal Care and Use Committee at the University of Nebraska.Experimental design. Hamsters (n ϭ 64) were randomly divided into five groups. Each group contained 13 hamsters (the 18:0 group contained 12 hamsters). Hamsters were...