Hypocholesterolemic Effects of Hydroxypropyl Methylcellulose Are Mediated by Altered Gene Expression in Hepatic Bile and Cholesterol Pathways of Male Hamsters
Hypocholesterolemic Effects of Hydroxypropyl Methylcellulose Are Mediated by Altered Gene Expression in Hepatic Bile and Cholesterol Pathways of Male Hamsters
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DOI：
10.3945/jn.109.118349
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发表时间：
2010-07-01
影响因子：
4.2
通讯作者：
Kim, Hyunsook
中科院分区：
文献类型：
--
作者：
Bartley, Glenn E.;Yokoyama, Wallace;Kim, Hyunsook
羟丙基甲基纤维素（HPMC）是一种半合成、不可发酵的可溶性膳食纤维，不被人体吸收，但其在肠腔中的存在会增加粪便脂肪、固醇和胆汁酸的排泄，并减少肠道胆固醇的吸收，所有这些都可能间接影响肝脏脂质代谢。我们测量了仓鼠的肝脏基因的表达，参与胆固醇，胆汁酸和脂肪酸代谢的饮食中含有39%的能量作为脂肪和5%的重量作为羟丙基甲基纤维素或微晶纤维素（对照）4周。与对照组相比，HPMC喂养的仓鼠体重增加明显更少，但摄食量没有差异。他们有显着降低血浆甘油三酯和总，极低密度脂蛋白，高密度脂蛋白和低密度脂蛋白胆固醇浓度和肝脏总脂质，总和游离胆固醇和甘油三酯浓度比对照组。与对照组相比，饲喂HPMC的仓鼠的CYP 7A 1（细胞色素P450 7A 1;对照组的8倍; P < 0.05）、CYP 51（羊毛甾醇14 α-脱甲基酶;对照组的5.3倍; P < 0.05）和HMG-CoAR（3-羟基-3-甲基戊二酰CoA还原酶;对照组的1.8倍; P < 0.05）的mRNA水平更高。对照组和HPMC组的血浆总胆固醇浓度与肝脏CYP 7A 1（r = -0.54; P < 0.05）、CYP 51（r = -0.79; P < 0.005）和HMG-CoAR（r = -0.75; P < 0.005）基因表达呈负相关。这表明HPMC补充影响胆固醇和胆汁酸合成。我们的数据证实，脂质代谢相关基因的肝脏表达改变，可能是由于调节粪便胆汁酸排泄和肠道胆固醇吸收，有助于HPMC的降脂作用。J.营养140：1255-1260，2010.
Hydroxypropyl methylcellulose (HPMC), a semisynthetic, nonfermentable soluble dietary fiber, is not absorbed by the body, but its presence in the intestinal lumen increases fecal fat, sterol, and bile acid excretions and decreases intestinal cholesterol absorption, all of which may indirectly affect hepatic lipid metabolism. We measured the expression of hepatic genes involved in cholesterol, bile acid, and fatty acid metabolism in hamsters fed diets containing 39% of energy as fat and 5% of weight as HPMC or microcrystalline cellulose (control) for 4 wk. HPMC-fed hamsters gained significantly less body weight than the control group but did not differ in food intake. They had significantly lower plasma triglyceride and total-, VLDL-, HDL-, and LDL-cholesterol concentrations and hepatic total lipid, total and free cholesterol and triglyceride concentrations than controls. Compared with controls, HPMC-fed hamsters had greater levels of mRNA for CYP7A1 (cytochrome P450 7A1; 8-fold of control; P < 0.05), CYP51 (lanosterol 14 alpha-demethylase; 5.3-fold of control; P < 0.05), and HMG-CoAR (3-hydroxy-3-methylglutaryl CoA reductase; 1.8-fold of control; P < 0.05). The plasma total cholesterol concentrations from both the control and HPMC groups were inversely correlated with expression of hepatic CYP7A1 (r = -0.54; P < 0.05), CYP51 (r = -0.79; P < 0.005), and HMG-CoAR (r = -0.75; P < 0.005) genes. This suggests that HPMC supplementation affected both cholesterol and bile acid synthesis. Our data confirm that altered hepatic expression of lipid metabolism-related genes, possibly due to modulation of fecal bile acid excretion and intestinal cholesterol absorption, contributes to the lipid-lowering effects of HPMC. J. Nutr. 140: 1255-1260, 2010.