Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-β via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-β)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.

中文翻译：

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补充 CLA 的饮食通过诱导产生 TGF-β 的巨噬细胞和 T 细胞来加速实验性结直肠癌。

已证明共轭亚油酸 (CLA) 可激活核受体 PPAR-γ 并调节代谢和免疫功能。尽管在全球范围内使用 CLA 膳食补充剂，但缺乏强有力的科学证据证明其所提出的有益作用。我们发现补充 CLA 的饮食减少了葡聚糖硫酸钠 (DSS) 诱导的结肠炎模型中的粘膜损伤和炎症浸润。补充 CLA 饮食的小鼠巨噬细胞中 PPAR-γ 的条件性缺失导致 CLA 的这种保护作用丧失，表明巨噬细胞介导的 PPAR-γ 依赖机制。然而，CLA 补充剂通过 PPAR-γ 激活诱导巨噬细胞和 T 细胞产生 TGF-β，从而显着恶化偶氮甲烷和 DSS 诱导的结直肠肿瘤形成。因此，PPAR-γ 的巨噬细胞特异性缺失或潜伏相关肽（LAP，一种膜结合的 TGF-β）表达细胞的体内中和消除了 CLA 的致癌作用。因此，CLA 的抗炎特性与预防结肠炎有关，但也与结直肠癌的发展有关。