Murakami Shigeru, Fujita Michiko, Nakamura Masakazu, Sakono Masanobu, Nishizono Shoko, Sato Masao, Imaizumi Katsumi, Mori Mari, Fukuda Nobuhiro
Department of Bioscience, Fukui Prefectural University, Fukui.
Department of Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki.
Clin Exp Pharmacol Physiol. 2016 Mar;43(3):372-8. doi: 10.1111/1440-1681.12534.
This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels.
本研究旨在探讨日粮牛磺酸对高胆固醇喂养大鼠胆固醇代谢的影响。将雄性斯普拉格-道利大鼠随机分为两个日粮组（每组n = 6）：含0.5%胆固醇和0.15%胆酸钠的高胆固醇日粮组，以及含5%（w/w）牛磺酸的高胆固醇日粮组。实验日粮喂养2周。补充牛磺酸可使血清和肝脏胆固醇水平分别降低37%和32%。与未处理大鼠相比，牛磺酸处理组大鼠粪便胆汁酸排泄显著增加。牛磺酸也使胆汁中胆汁酸浓度升高。补充牛磺酸使牛磺酸结合型胆汁酸增加61%，甘氨酸结合型胆汁酸减少53%，导致甘氨酸/牛磺酸（G/T）比值显著降低。在牛磺酸结合型胆汁酸中，胆酸和脱氧胆酸显著增加。在肝脏中，补充牛磺酸使胆汁酸合成限速酶肝胆固醇7α-羟化酶（CYP7A1）的mRNA表达和酶活性分别增加3倍和2倍。牛磺酸还降低了酰基辅酶A：胆固醇酰基转移酶（ACAT）和微粒体甘油三酯转移蛋白（MTP）的酶活性。这些观察结果表明，补充牛磺酸可增加牛磺酸结合型胆汁酸的合成和排泄，并通过提高CYP7A1的表达和活性刺激胆固醇向胆汁酸的分解代谢。这可能减少胆固醇酯化和极低密度脂蛋白（VLDL）分泌的脂蛋白组装，从而导致血清和肝脏胆固醇水平降低。
