Moriceau S, Besson C, Levrat M A, Moundras C, Rémésy C, Morand C, Demigné C
Unité Maladies Métaboliques & Micronutriments, INRA de Theix, St-Genès-Champanelle, France.
Lipids. 2000 Apr;35(4):437-44. doi: 10.1007/s11745-000-542-x.
Soluble fibers such as guar gum (GG) may exert cholesterol-lowering effects. It is generally accepted that bile acid (BA) reabsorption in portal blood is reduced, thus limiting the capacity of BA to down-regulate liver cholesterol 7alpha-hydroxylase, the rate-limiting enzyme of BA synthesis. In the present work, rats were adapted to fiber-free (FF) or 5% GG diets (supplemented or not with 0.25% cholesterol), to investigate various aspects of enterohepatic BA cycling. GG in the diet at a level of 5% elicited a significant lowering of plasma cholesterol during the absorptive period, in cholesterol-free (-13%) or 0.25% cholesterol (-20%) diet conditions. In rats adapted to the GG diets, the small intestinal and cecal BA pools and the ileal vein-artery difference for BA were markedly enhanced; reabsorption in the cecal vein was also enhanced in these rats. [14C]Taurocholate absorption, determined in perfused ileal segments, was not significantly different in rats adapted to the FF or GG diet, suggesting that a greater flux of BA in the ileum might support a greater ileal BA reabsorption in rats adapted to the GG diet. In contrast, capacities for [14C]cholate absorption from the cecum at pH 6.5 were higher in rats adapted to the GG diet than to the FF diet. Acidification of the bulk medium in isolated cecum (from pH 7.1 down to pH 6.5 or 5.8) or addition of 100 mM volatile fatty acids was also found to stimulate cecal [14C]cholate absorption. These factors could contribute to accelerated cecal BA absorption in rats fed the GG diet. The effects of GG on steroid fecal excretion thus appear to accompany a greater intestinal BA absorption and portal flux to the liver. These results suggest that some mechanisms invoked to explain cholesterol-lowering effect of fibers should be reconsidered.
瓜尔胶(GG)等可溶性纤维可能具有降低胆固醇的作用。人们普遍认为,门静脉血中胆汁酸(BA)的重吸收减少,从而限制了BA下调肝脏胆固醇7α-羟化酶(BA合成的限速酶)的能力。在本研究中,将大鼠分别饲喂无纤维(FF)或5% GG日粮(添加或不添加0.25%胆固醇),以研究肠肝循环中BA的各个方面。在无胆固醇(-13%)或0.25%胆固醇(-20%)日粮条件下,5%水平的日粮GG在吸收期可显著降低血浆胆固醇。在适应GG日粮的大鼠中,小肠和盲肠的BA池以及BA的回肠静脉-动脉差值显著增加;这些大鼠盲肠静脉的重吸收也增强。在灌注的回肠段测定的[14C]牛磺胆酸盐吸收,在适应FF或GG日粮的大鼠中没有显著差异,这表明回肠中BA通量的增加可能支持适应GG日粮的大鼠回肠BA重吸收增加。相比之下,适应GG日粮的大鼠从盲肠吸收[14C]胆酸盐的能力高于适应FF日粮的大鼠。还发现,分离的盲肠中大量培养基酸化(从pH 7.1降至pH 6.5或5.8)或添加100 mM挥发性脂肪酸可刺激盲肠[14C]胆酸盐吸收。这些因素可能有助于加速饲喂GG日粮的大鼠盲肠BA吸收。因此,GG对类固醇粪便排泄的影响似乎伴随着肠道BA吸收增加和门静脉向肝脏的通量增加。这些结果表明,一些用于解释纤维降胆固醇作用的机制应重新考虑。