Chen L D, Kushwaha R S, Rice K S, Carey K D, McGill H C
Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Metabolism. 1998 Jun;47(6):731-8. doi: 10.1016/s0026-0495(98)90038-5.
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.
我们之前的研究发现，与高低密度脂蛋白（LDL）反应型狒狒相比，低LDL反应型狒狒在食用高胆固醇和高脂肪（HCHF）饮食时，肝脏固醇27-羟化酶活性更高。本研究旨在确定低反应型狒狒的固醇27-羟化酶肝外活性是否也更高，并评估该酶是否在蛋白质水平受到调节。我们测量了6只低反应型和6只高反应型狒狒在基础饮食和HCHF饮食条件下的肝脏固醇27-羟化酶活性、蛋白质水平以及血浆27-羟胆固醇浓度。我们还比较了食用HCHF饮食的高反应型和低反应型狒狒肾上腺中的固醇27-羟化酶活性以及血液淋巴细胞中的27-羟胆固醇浓度。在HCHF饮食条件下，低反应型狒狒的血浆27-羟胆固醇浓度、肝脏固醇27-羟化酶活性和蛋白质水平迅速升高，而高反应型狒狒则不然。在缺乏脂蛋白的血清（LPDS）存在下培养的低反应型狒狒的血液淋巴细胞中的胆固醇浓度低于高反应型狒狒。向血液淋巴细胞培养基中添加外源性27-羟胆固醇可降低细胞胆固醇浓度。在HCHF饮食6周后，血浆27-羟胆固醇、肝脏固醇27-羟化酶活性和蛋白质水平与血浆极低密度脂蛋白（VLDL）+低密度脂蛋白（LDL）胆固醇浓度以及VLDL + LDL/高密度脂蛋白（HDL）胆固醇比值呈负相关，但在普通饮食条件下则无此相关性。结果表明，肝脏和肝外组织中的固醇27-羟化酶活性减弱了狒狒对饮食的反应性，且该酶活性不受蛋白质比活性的调节。
