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.
Chen
L D
LD
Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Kushwaha
R S
RS
Rice
K S
KS
Carey
K D
KD
McGill
H C
HC
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003577:Cytochrome P-450 Enzyme System / Q000097:blood / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008214:Lymphocytes / Q000378:metabolism; D009994:Osmolar Concentration; D010215:Papio / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000097:blood / Q000378:metabolism*
D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008074:Lipoproteins; C030104:lipoprotein cholesterol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase