Increasing amounts of dietary myristic acid modify the plasma cholesterol level and hepatic mass of scavenger receptor BI without affecting bile acid biosynthesis in hamsters.

The purpose of this study was to analyze the effects of increasing amounts of dietary myristic acid (0.03 to 4.2% of the total dietary energy) on the plasma and hepatic cholesterol metabolism. Six groups of hamsters received semi-purified diets containing 0.05% cholesterol and 12.5% lipids and differing only by the nature of the triglycerides (Safflower oil, lard, lard/coconut oil (1:1), milk fat, milk fat/coconut oil (1:1), coconut oil) for 3 weeks. A positive regression between the plasma cholesterol level and the dietary myristic acid level was observed (r = 0.60, P < 0.0001). However, it is noteworthy that the increase in plasma total cholesterol only reflects an increase in the level of HDL-cholesterol. In parallel, the mass SR-BI decreased linearly with the increased level of myristic acid in the diet, whereas the LDL-R did not change. This study shows that increasing amounts of myristic acid (0.03 to 4.2%) do not alter the cholesterol or bile acid metabolism and increase only the HDL-C.

Dietary myristic acid modifies the HDL-cholesterol concentration and liver scavenger receptor BI expression in the hamster.

The influence of myristic acid in a narrow physiological range (0.5 to 2.4% of total dietary energy) on the plasma and hepatic cholesterol metabolism was investigated in the hamster. The hamsters were fed on a diet containing 12.5 g fat/100 g and 0.05 g cholesterol/100 g with 0.5% myristic acid (LA diet) for 3 weeks (pre-period). During the following 3 weeks (test period), they were divided into four dietary groups with 0.5% (LA), 1.2% (LM), 1.8% (ML) or 2.4% (M) myristic acid. Finally, half the hamsters in each group were again fed the LA diet for another 3 weeks (post-period). At the end of the test period, the hepatic expression of the scavenger receptor BI (SR-BI) was lower in the LM, ML and M groups than in the LA group whereas the hepatic cholesteryl ester concentration was higher. Cholesterol 7alpha hydroxylase activity was lower in the ML and M groups than in the LA and LM groups while the sterol 27 hydroxylase and 3-hydroxy-3-methyl glutaryl coenzyme A reductase activities were not modulated by dietary myristic acid. This is the first time a negative correlation has been observed between the HDL-cholesterol concentration and the hepatic mass of SR-BI (r -0.69; P<0.0001) under physiological conditions. An inverse linear regression was also shown between SR-BI and the percentage of myristic acid in the diet (r -0.75; P<0.0001). The hepatic mass of SR-BI in the M group had increased at the end of the post-period compared with the test-period values. The present investigation shows that myristic acid modulates HDL-cholesterol via a regulation of the SR-BI expression.

Effects of dietary 27-hydroxycholesterol on cholesterol metabolism and bile acid biosynthesis in the hamster.

27-hydroxycholesterol (27OH-Chol) is an important endogenous oxysterol resulting from the action of sterol 27-hydroxylase (CYP27A1) on cholesterol in the liver and numerous extrahepatic tissues. It may act as a modulator of cholesterol and bile acid metabolism. The effects of 27OH-Chol on the main enzymes and receptors of cholesterol metabolism were investigated by feeding male hamsters a diet supplemented with 27OH-Chol (0.1% w/w) for 1 week. Intestinal scavenger class B, type I (SR-BI) protein level was decreased (-65%), but hepatic expression was increased (+34%). Liver 3beta-hydroxy-3beta-methyl glutaryl coenzyme A reductase (-58%), cholesterol 7alpha-hydroxylase (-54%), oxysterol 7alpha-hydroxylase (-44%), and sterol 12alpha-hydroxylase (-70%) activities were all decreased. Bile acid composition was changed (fourfold increase in the chenodeoxycholic/cholic acid ratio). This study demonstrates that dietary 27OH-Chol modulates major enzymes of cholesterol metabolism and alters the biliary bile acid profile, making it more hydrophobic, at least at this level of intake. Its effects on SR-BI protein levels are organ dependent. The properties of 27OH-Chol or its metabolites on cholesterol metabolism probably result from the activation of specific transcription factors.