High Dietary Niacin May Increase Prostaglandin Formation but Does Not Increase Tumor Formation in ApcMin/+ Mice
High Dietary Niacin May Increase Prostaglandin Formation but Does Not Increase Tumor Formation in ApcMin/+ Mice
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DOI：
10.1080/01635581.2011.590266
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发表时间：
2011-08-01
影响因子：
2.9
通讯作者：
Lin, Henry J.
中科院分区：
文献类型：
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作者：
Kwong, Alan M.;Tippin, Brigette L.;Lin, Henry J.
高剂量的烟酸（烟酸）用于治疗血脂异常引起潮红，由于高水平的前列腺素D-2 （PGD(2)）。GPR109A是一种g蛋白偶联受体，会引发皮肤潮红。除了促进PGD(2)，烟酸结合GPR109A激活整个前列腺素级联反应。我们发现GPR109A存在于整个胃肠道。在1%烟酸饮食和对照饮食之间交替的小鼠，在烟酸饮食中有更高的尿前列腺素E-2 （PGE(2)）代谢物水平（增加2.8倍；95%置信区间，1.8-3.9）。PGE(2)促进肠内肿瘤，而PGD(2)可能具有相反的作用，根据我们的报告显示转基因造血前列腺素D合成酶抑制Apc（Min/+）小鼠肠腺瘤。为了确定是肿瘤生长还是肿瘤抑制，我们给Apc（Min/+）小鼠喂食1%烟酸饮食并评估肿瘤的发展。1%烟酸饮食不影响Apc（Min/+）小鼠14周组织学评分的肿瘤数量（烟酸组33只，对照组33只）。虽然烟酸刺激各种前列腺素的产生，但我们的研究结果支持一种解释，即在该模型中，非常高的烟酸摄入量与肠道肿瘤有关。
High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D-2 (PGD(2)). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD(2), niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E-2 (PGE(2)) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8-3.9). PGE(2) promotes tumors in the intestines, whereas PGD(2) may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc(Min/+) mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc(Min/+) mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc(Min/+) mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.