小柯机器人

美国伊利诺伊大学芝加哥分校Nissim Hay研究团队发现，在基质脱落和肿瘤进展过程中，CD36通过选择性吸收单不饱和脂肪酸(MUFA)维持脂质稳态。2023年10月17日出版的《细胞—代谢》杂志发表了这项成果。

在基质脱落过程中，内质网（ER）应激减少了SCD1蛋白的产生，导致脂质饱和度增加。随后，CD36由p38和AMPK依赖的方式诱导产生，促进对单不饱和脂肪酸的优先摄取，从而维持饱和脂肪酸（SFAs）和MUFA之间的平衡。在附着细胞中，CD36棕榈酰化是MUFA吸收和保护细胞免受棕榈酸酯诱导脂毒性的基础。

在乳腺癌小鼠模型中，CD36缺失会诱发ER应激，同时减弱高脂饮食（HFD）的促进转移效应，只有棕榈酰化缺失的CD36才能挽救这种效应。最后，AMPK缺陷的肿瘤细胞中CD36表达减少，转移能力受损，但异位CD36表达可恢复其转移潜力。该研究结果表明，CD36并不会促进HFD诱导的肿瘤发生，而是通过防止SFA诱导的脂肪毒性发挥促癌作用。

据悉，HFD通过增加饱和脂肪酸的摄入促进转移。脂肪酸转运体CD36与这一过程有关，但人们对CD36的功能还缺乏详细了解。

附：英文原文

Title: CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression

Author: Alexander R. Terry, Veronique Nogueira, Hyunsoo Rho, Gopalakrishnan Ramakrishnan, Jing Li, Soeun Kang, Koralege C. Pathmasiri, Sameer Ahmed Bhat, Liping Jiang, Shafi Kuchay, Stephanie M. Cologna, Nissim Hay

Issue&Volume: 2023-10-17

Abstract: A high-fat diet (HFD) promotes metastasis through increased uptake of saturated fattyacids (SFAs). The fatty acid transporter CD36 has been implicated in this process,but a detailed understanding of CD36 function is lacking. During matrix detachment,endoplasmic reticulum (ER) stress reduces SCD1 protein, resulting in increased lipidsaturation. Subsequently, CD36 is induced in a p38- and AMPK-dependent manner to promotepreferential uptake of monounsaturated fatty acids (MUFAs), thereby maintaining abalance between SFAs and MUFAs. In attached cells, CD36 palmitoylation is requiredfor MUFA uptake and protection from palmitate-induced lipotoxicity. In breast cancermouse models, CD36-deficiency induced ER stress while diminishing the pro-metastaticeffect of HFD, and only a palmitoylation-proficient CD36 rescued this effect. Finally,AMPK-deficient tumors have reduced CD36 expression and are metastatically impaired,but ectopic CD36 expression restores their metastatic potential. Our results suggestthat, rather than facilitating HFD-driven tumorigenesis, CD36 plays a supportive roleby preventing SFA-induced lipotoxicity.

DOI: 10.1016/j.cmet.2023.09.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00368-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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