小组定义了一种营养信号机制，涉及脂肪酸结合蛋白5 （FABP5）和雷帕霉素复合物1 （mTORC1）的机制靶点，该靶点由必需多不饱和脂肪酸(PUFA) ω-6亚油酸（LA）激活。FABP5直接结合到mTOR的调控相关蛋白（Raptor）上，增强功能性mTORC1的形成和底物结合，最终汇聚到mTOR信号传导增加和增殖上。与受体阳性乳腺癌患者相比，三阴性乳腺癌患者的肿瘤和血清中FABP5蛋白的含量增加，这突出了其作为生物标志物的潜在作用，可介导该疾病亚型中ω-6 LA摄入的细胞反应。
研究人员表示，饮食会影响细胞对常量营养素的利用，虽然对饮食中葡萄糖和氨基酸的感知机制已经很好地描述了，但对脂质的感知却知之甚少。
附：英文原文
Title: Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling
Author: Nikos Koundouros, Michal J. Nagiec, Nayah Bullen, Evan K. Noch, Guillermo Burgos-Barragan, Zhongchi Li, Long He, Sungyun Cho, Bobak Parang, Dominique Leone, Eleni Andreopoulou, John Blenis
Issue&Volume: 2025-03-14
Abstract: Diet influences macronutrient availability to cells, and although mechanisms of sensing dietary glucose and amino acids are well characterized, less is known about sensing lipids. We defined a nutrient signaling mechanism involving fatty acid–binding protein 5 (FABP5) and mechanistic target of rapamycin complex 1 (mTORC1) that is activated by the essential polyunsaturated fatty acid (PUFA) ω-6 linoleic acid (LA). FABP5 directly bound to the regulatory-associated protein of mTOR (Raptor) to enhance formation of functional mTORC1 and substrate binding, ultimately converging on increased mTOR signaling and proliferation. The amounts of FABP5 protein were increased in tumors and serum from triple-negative compared with those from receptor-positive breast cancer patients, which highlights its potential role as a biomarker that mediates cellular responses to ω-6 LA intake in this disease subtype.
DOI: adm9805
Source: https://www.science.org/doi/10.1126/science.adm9805