METABOLIC MECHANISMS FOR RESPONSES TO DIETARY-CHOLESTEROL AND FAT IN HIGH AND LOW LDL RESPONDING BABOONS (PAPIO SP)

These studies were conducted to determine how plasma low density lipop rotein (LDL) cholesterol levels respond to dietary cholesterol, fed in increasing amounts with either corn oil or coconut oil diets, in high as compared to low LDL responding baboons; and to determine how apoli poprotein (ape) B transcription levels are modulated in response to di etary lipids. Eight high and eight low LDL responding pedigreed adult baboons, balanced for sire, age, sex, and weight, were challenged for successive 7-week periods with increasing levels of dietary cholestero l combined with either coconut oil or corn oil. At the end of each die tary period, plasma and lipoprotein lipids, apoB, apoA-I, and hepatic mRNA levels for apolipoproteins were measured. As dietary cholesterol increased, plasma cholesterol concentrations (mostly LDL cholesterol) increased in both phenotypes and with bath types of fat, but phenotypi c differences were greater with coconut oil. There was not a consisten t dose-response relationship of plasma or LDL cholesterol levels to in creasing intakes of dietary cholesterol. Neither dietary cholesterol, type of dietary fat, nor LDL phenotype affected hepatic apoB or apoE m RNA levels. In a second experiment to resolve the inconsistent dose-re sponse to dietary cholesterol, we fed the animals varying levels of di etary cholesterol combined with coconut oil, and separated the challen ge periods with interventing 12-week chow periods. Plasma and LDL chol esterol and apoB concentrations rose consistently with increasing diet ary cholesterol, and the slope of the increase diminished at the highe r doses. The results suggest that genetic differences in the initial r esponse of LDL cholesterol to dietary cholesterol and saturated fatty acids are not due to the differences in hepatic transcription of apoB, and that the preceding dietary intake of cholesterol and saturated fa tty acids is a major determinant of the response of plasma lipids and the associated metabolic processes to a dietary challenge. The respons e of baboon plasma LDL cholesterol concentrations to dietary cholester ol, when fed with saturated fatty acids, is similar to that of humans.