Effect of dietary lipids on hepatic and extrahepatic sterol 27-hydroxylase activity in high- and low-responding baboons.

Our previous studies found that low low-density lipoprotein (LDL)-responding baboons compared with high LDL-responding baboons have higher hepatic sterol 27-hydroxylase activity when consuming a high-cholesterol and high-fat (HCHF) diet. The present studies were conducted to determine whether the extrahepatic activity of sterol 27-hydroxylase is also higher in low-responding baboons and to assess whether the enzyme is regulated at the protein level. We measured the hepatic sterol 27-hydroxylase activity and protein level and plasma 27-hydroxycholesterol concentration in six low- and six high-responding baboons on both the basal and the HCHF diet. We also compared the sterol 27-hydroxylase activity in the adrenal gland and 27-hydroxycholesterol concentration in blood lymphocytes from high- and low-responding baboons consuming the HCHF diet. With the HCHF diet, the plasma 27-hydroxycholesterol concentration and hepatic sterol 27-hydroxylase activity and protein level increased rapidly in low responders, but not in high responders. Blood lymphocytes of low-responding baboons cultured in the presence of lipoprotein-deficient serum (LPDS) had lower cholesterol concentrations than those from high-responding baboons. Addition of exogenous 27-hydroxycholesterol to the culture medium of blood lymphocytes decreased the cellular cholesterol concentration. Plasma 27-hydroxycholesterol and hepatic sterol 27-hydroxylase activity and protein levels were negatively correlated with the plasma VLDL + LDL cholesterol concentration and VLDL + LDL/HDL cholesterol ratio after 6 weeks on the HCHF diet, but not on the chow diet. The results suggest that sterol 27-hydroxylase activity in both hepatic and extrahepatic tissues attenuates the dietary responsiveness in baboons, and the enzyme activity is not regulated by the specific activity of the protein.