Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Eur J Gastroenterol Hepatol. 2009 Jun;21(6):642-9. doi: 10.1097/meg.0b013e328321b0c8.
Increasing HDL cholesterol concentrations by stimulating de-novo apolipoprotein A-I (apoA-I) production in the liver and/or in the small intestine is a potential strategy to reduce coronary heart disease risk. Although there is quite some knowledge concerning regulatory effects in the liver, less is known concerning potential agents that could elevate de-novo apoA-I production in the small intestine.
Therefore, we compared side-by-side effects of various peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, retinoid-X-receptor alpha, and farnesoid-X-receptor agonists on de-novo apoA-I production in differentiated CaCo-2 and HepG2 cells.
For PPARa agonists, we showed that GW7647 elevated apoA-I concentrations in the medium of both cell models, whereas WY14643 elevated only de-novo apoA-I concentrations in differentiated CaCo-2 cells. Unexpectedly, fenofibric acid lowered apoA-I medium concentrations in both cell lines, which could not be explained by a lack of PPAR transactivation or a lack of retinoid-X-receptor a activation. For farnesoid-X-receptor agonists, chenodeoxycholic acid strongly reduced apoA-I concentrations both in differentiated CaCo-2 and HepG2 cells, whereas GW4064 and taurocholate only lowered apoA-I in CaCo-2 cells (GW4064) or in HepG2 cells (taurocholate). However, overall effects of all individual components on apoA-I production in differentiated CaCo-2 and HepG2 cells were highly correlated (r = 0.68; P = 0.037; N=9).
We conclude that differentiated CaCo-2 cells are suitable models to study de-novo small intestinal apoA-I production in vitro enabling the possibility to screen for potential bioactive dietary components. This cell model may also determine small-intestinal-specific effects, as some discrepancy was found between both cell models.
通过刺激肝脏和/或小肠中载脂蛋白 A-I（apoA-I）的从头合成来增加高密度脂蛋白胆固醇浓度是降低冠心病风险的一种潜在策略。尽管人们对肝脏的调节作用有相当多的了解，但对于可能提高小肠中从头合成 apoA-I 的潜在药物知之甚少。
因此，我们比较了各种过氧化物酶体增殖物激活受体（PPAR）α、PPARγ、视黄醇 X 受体α和法尼醇 X 受体激动剂对分化的 CaCo-2 和 HepG2 细胞中从头合成 apoA-I 的并排作用。
对于 PPARa 激动剂，我们表明 GW7647 增加了两种细胞模型中apoA-I 的浓度，而 WY14643 仅增加了分化的 CaCo-2 细胞中从头合成 apoA-I 的浓度。出乎意料的是，非诺贝特酸降低了两种细胞系中 apoA-I 的介质浓度，这不能用缺乏 PPAR 反式激活或缺乏视黄醇 X 受体 a 激活来解释。对于法尼醇 X 受体激动剂，鹅脱氧胆酸强烈降低了分化的 CaCo-2 和 HepG2 细胞中 apoA-I 的浓度，而 GW4064 和牛磺胆酸盐仅降低了 CaCo-2 细胞（GW4064）或 HepG2 细胞（牛磺胆酸盐）中的 apoA-I。然而，所有单个成分对分化的 CaCo-2 和 HepG2 细胞中 apoA-I 产生的总体影响高度相关（r = 0.68；P = 0.037；N = 9）。
我们得出结论，分化的 CaCo-2 细胞是体外研究从头合成小肠 apoA-I 的合适模型，使筛选潜在生物活性膳食成分成为可能。该细胞模型也可能确定小肠特异性效应，因为在两种细胞模型之间发现了一些差异。
