The most recent American Dietary Guidelines (2020–2025) recommend shifting dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in oils regulate immune cell function and cancer risk remains unclear. Here we demonstrated that high-fat diets (HFD) rich either in OA or LA induced a similar degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor growth. LA impaired antitumor T-cell responses by promoting naïve T-cell apoptosis and inhibiting TNFα production. While exogenous OA and LA were taken up by T cells with similar efficacy, only LA induced significant mitochondrial reactive oxygen species production and lipid peroxidation. Importantly, naïve T cells predominantly expressed epidermal fatty acid binding protein (E-FABP), which is central in facilitating LA mitochondrial transport and cardiolipin incorporation. Genetic depletion of E-FABP rescued LA-impaired T-cell responses and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these data suggest that dietary oils high in LA promote mammary tumors by inducing E-FABP–mediated T-cell dysfunction. Significance: These findings suggest that modulation of dietary oil composition and inhibition of E-FABP activity may represent novel strategies to enhance T-cell function in the prevention and treatment of obesity-associated cancers.

中文翻译：

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富含亚油酸的膳食脂肪通过诱导 E-FABP 介导的线粒体功能障碍来损害抗肿瘤 T 细胞反应


最新的美国膳食指南（2020-2025）建议将膳食脂肪从固体饱和脂肪转变为不饱和油。膳食油含有不同的不饱和脂肪酸（UFA）成分。油酸 (OA) 和亚油酸 (LA) 是膳食油中最常见的 UFA。油中的个别 UFA 如何调节免疫细胞功能和癌症风险仍不清楚。在这里，我们证明富含 OA 或 LA 的高脂饮食 (HFD) 会引起类似程度的小鼠肥胖，但富含 LA 的 HFD 特别促进乳腺肿瘤的生长。 LA 通过促进幼稚 T 细胞凋亡和抑制 TNFα 产生来损害抗肿瘤 T 细胞反应。虽然 T 细胞吸收外源 OA 和 LA 具有相似的功效，但只有 LA 诱导显着的线粒体活性氧产生和脂质过氧化。重要的是，幼稚 T 细胞主要表达表皮脂肪酸结合蛋白 (E-FABP)，它对于促进 LA 线粒体转运和心磷脂掺入至关重要。 E-FABP 的基因缺失可以挽救 LA 受损的 T 细胞反应，并抑制富含 LA 的 HFD 相关乳腺肿瘤生长。总的来说，这些数据表明，富含 LA 的膳食油通过诱导 E-FABP 介导的 T 细胞功能障碍而促进乳腺肿瘤。意义：这些发现表明，调节膳食油成分和抑制 E-FABP 活性可能代表增强 T 细胞功能预防和治疗肥胖相关癌症的新策略。