Conjugated Linoleic Acid Ameliorates Inflammation-Induced Colorectal Cancer in Mice through Activation of PPARγ
Conjugated Linoleic Acid Ameliorates Inflammation-Induced Colorectal Cancer in Mice through Activation of PPARγ
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DOI：
10.3945/jn.109.115642
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发表时间：
2010-03-01
影响因子：
4.2
通讯作者：
Bassaganya-Riera, Josep
中科院分区：
文献类型：
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作者：
Evans, Nicholas P.;Misyak, Sarah A.;Bassaganya-Riera, Josep
共轭亚油酸（CLA）对实验性炎症性肠病具有保护作用，并有望作为小鼠结直肠癌（CRC）的化学预防剂，尽管其对肠道恶性肿瘤发挥有益作用的机制尚未完全了解。免疫细胞和上皮细胞中缺乏PPAR γ的小鼠和表达PPAR γ的同窝出生的小鼠被喂食对照或补充CLA的（1 g CLA/100 g）饮食，以确定PPAR γ在炎症诱导的CRC中的作用。为了诱导肿瘤形成和结肠炎，分别用氧化偶氮甲烷处理小鼠，然后用2%葡聚糖硫酸钠激发。饮食CLA改善了疾病活动，减少结肠炎，并防止在表达PPAR γ的floxed小鼠的腺癌形成，但在组织特异性PPAR γ-null小鼠。无论基因型如何，膳食CLA补充剂均显著降低了肠系膜淋巴结（MLN）中巨噬细胞的百分比，并增加了表达PPAR γ的MLN中的调节性T细胞数量，但在组织特异性PPAR γ缺失小鼠中则不然。在CLA喂养的表达PPAR γ的小鼠中，结肠肿瘤坏死因子α mRNA的表达被显著抑制。这项研究表明，共轭亚油酸改善结肠炎，并防止肿瘤形成的一部分，通过过氧化物酶体增殖物激活受体γ依赖性机制。J·纳特140：515-521，2010.
Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPAR gamma in immune and epithelial cells and PPAR gamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPAR gamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPAR gamma-expressing floxed mice but not in the tissue-specific PPAR gamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPAR gamma-expressing, but not in the tissue-specific, PPAR gamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPAR gamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPAR gamma-dependent mechanism. J. Nutt. 140: 515-521, 2010.