RESUMO
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.
Assuntos
Anticolesterolemiantes/farmacologia , Ácidos e Sais Biliares/biossíntese , Colesterol na Dieta/efeitos adversos , Colesterol na Dieta/metabolismo , Dieta Hiperlipídica/efeitos adversos , Taurina/farmacologia , Animais , Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Colesterol na Dieta/sangue , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hidroximetilglutaril-CoA Redutases/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Esterol O-Aciltransferase/metabolismoRESUMO
AIM: The high-density lipoprotein cholesterol(HDL-C) level is a major negative risk factor for atherosclerotic diseases dependent on various lifestyle parameters. Changes in the lifestyle of Japanese individuals over the past several decades is believed to have increased their total cholesterol levels and the incidence of cardiovascular disease in Japan. It is therefore important to assess the long-term trends in the HDL-C levels with respect to public health in the community. METHODS: In this study, accumulated data for the serum/plasma HDL-C levels published in cohort studies and obtained during health checkup programs in Japan were analyzed with respect to timedependent changes. RESULTS: The levels of HDL-C have continuously and significantly increased over the past 20 years by 12-15% according to the National Health and Nutrition Study, other cohort studies and commercially available data. On the other hand, the non-HDL-cholesterol levels demonstrated no changes or only a slight decrease during the same period. This finding is consistent with several sets of data obtained from health checkup programs. The commercially measured levels of serum apoA-I, an independent parameter of serum HDL, also showed a similar long-term increase, supporting the above findings. CONCLUSION: We concluded that the serum/plasma HDL concentrations in Japanese individuals, selectively, have increased continuously and significantly over the past 20 years or more. The reasons for this phenomenon and the consequent public health outcomes have yet to be investigated.