Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes and precursors for signalling molecules. Here we show that these biological compounds also regulate gene expression and that they do so by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. The data indicate that these activities of LCFA are mediated by FABP5, which delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. We show further that, by concomitantly promoting the activation of RAR and inhibiting the activation of PPARβ/δ, SLCFA suppress the oncogenic properties of FABP5-expressing carcinoma cells in cultured cells and in vivo. The observations suggest that compounds that inhibit FABP5 may constitute a new class of drugs for therapy of certain types of cancer.

中文翻译：

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饱和脂肪酸通过靶向脂肪酸结合蛋白5来调节视黄酸信号传导并抑制肿瘤发生。

长链脂肪酸（LCFA）可用作能源，细胞膜的成分和信号分子的前体。在这里，我们表明这些生物化合物还调节基因表达，并且它们通过控制视黄酸（RA）激活的核受体RAR和PPARβ/δ的转录活性来调节基因表达。数据表明，LCFA的这些活性是由FABP5介导的，FABP5将配体从细胞溶质传递至核PPARβ/δ。饱和和不饱和LCFA（SLCFA，ULCFA）都结合到FABP5，从而取代RA并将其转移到RAR。然而，尽管SLCFA抑制，ULCFA激活FABP5 /PPARβ/δ途径。我们进一步证明，通过同时促进RAR的激活和抑制PPARβ/δ的激活，SLCFA在培养的细胞和体内抑制表达FABP5的癌细胞的致癌特性。观察结果表明，抑制FABP5的化合物可能构成治疗某些类型癌症的新型药物。