Mezei Orsolya, Li Yilan, Mullen Eimear, Ross-Viola Jennifer S, Shay Neil F
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
Physiol Genomics. 2006 Jun 16;26(1):8-14. doi: 10.1152/physiolgenomics.00155.2005. Epub 2006 Feb 28.
Intake of soy protein has been associated with improvements in lipid metabolism, with much attention being focused on the serum cholesterol-lowering property of soy. The component or components of soy that are responsible for improvements in lipid metabolism have been investigated and their specific actions debated. One component, the isoflavones, has been shown to have weak estrogenic activity, and recently, several research groups have suggested that isoflavones are activating peroxisome proliferator-activated receptors (PPARs). The three different isoforms of PPARs (alpha, gamma, and delta) have overlapping tissue distributions and functions associated with lipid metabolism. The goal of the present study was to investigate the hypothesis that the effect of isoflavones is mediated through the PPARalpha receptor. Male and female 129/Sv mice were obtained, including both wild-type and genetically altered PPARalpha knockout mice. Groups of mice were fed high-fat atherogenic diets containing soy protein +/- isoflavones and PPARalpha agonist fenofibrate for 6 wk. At the end of 6 wk, serum and tissue lipid levels were measured along with hepatic gene expression. Most notably, serum triglycerides were reduced by isoflavone consumption. Compared with intake of a low-isoflavone basal diet, isoflavone intake reduced serum triglyceride levels by 36 and 52% in female and male wild-type mice, respectively, compared with 55 and 52% in fenofibrate-treated mice. Isoflavones also improved serum triglyceride levels in knockout mice, whereas fenofibrate did not, suggesting that two different regulatory mechanisms may be affected by isoflavone intake. Isoflavone intake resembled action of fenofibrate on PPARalpha-regulated gene expression, although less robustly compared with fenofibrate. We suggest that, at the levels consumed in this study, isoflavone intake is altering lipid metabolism in a manner consistent with activation of PPARalpha and also via a PPARalpha-independent mechanism as well.
摄入大豆蛋白与脂质代谢改善有关，大豆降血清胆固醇的特性备受关注。人们对大豆中负责脂质代谢改善的一种或多种成分进行了研究，并对其具体作用展开了争论。其中一种成分异黄酮已被证明具有弱雌激素活性，最近，几个研究小组表明异黄酮可激活过氧化物酶体增殖物激活受体（PPARs）。PPARs的三种不同亚型（α、γ和δ）具有重叠的组织分布以及与脂质代谢相关的功能。本研究的目的是探讨异黄酮的作用是通过PPARα受体介导的这一假说。获取了雄性和雌性129/Sv小鼠，包括野生型和基因改造的PPARα基因敲除小鼠。将小鼠分组，喂食含大豆蛋白±异黄酮和PPARα激动剂非诺贝特的高脂肪致动脉粥样硬化饮食6周。在6周结束时，测量血清和组织脂质水平以及肝脏基因表达。最值得注意的是，食用异黄酮可降低血清甘油三酯水平。与低异黄酮基础饮食的摄入量相比，异黄酮摄入量使雌性和雄性野生型小鼠的血清甘油三酯水平分别降低了36%和52%，而非诺贝特处理的小鼠分别降低了55%和52%。异黄酮也改善了基因敲除小鼠的血清甘油三酯水平，而异非诺贝特则没有，这表明异黄酮摄入可能影响两种不同的调节机制。异黄酮摄入量对PPARα调节的基因表达的作用类似于非诺贝特，尽管与非诺贝特相比作用较弱。我们认为，在本研究中所摄入的水平下，异黄酮摄入量以一种与PPARα激活一致的方式改变脂质代谢，并且还通过一种不依赖PPARα的机制。
