美国圣路易斯华盛顿大学Gary J. Patti研究小组发现，膳食果糖通过器官间脂质转移间接促进肿瘤生长。相关论文于2024年12月4日在线发表在《自然》杂志上。

研究人员发现，果糖补充可以在黑色素瘤、乳腺癌和宫颈癌的动物模型中促进肿瘤生长，而不会引起体重增加或胰岛素抵抗。癌细胞本身由于不表达酮己糖激酶-C（KHK-C），无法将果糖作为营养物质直接利用。初级肝细胞则表达KHK-C，导致果糖分解并排泄多种脂质种类，包括溶血磷脂酰胆碱（LPC）。

在共培养实验中，肝细胞衍生的LPC被癌细胞摄取，并用于合成磷脂酰胆碱，这是细胞膜的主要磷脂。体内实验中，高果糖玉米糖浆的补充使血清中几种LPC种类的水平增加了七倍以上。将LPC注入小鼠体内足以增加肿瘤生长。

酮己糖激酶的药理学抑制对癌细胞没有直接影响，但它降低了循环LPC的水平，并阻止了果糖介导的肿瘤生长。这些发现揭示了果糖补充通过增加循环营养物质（如LPC），从而通过细胞非自主机制促进肿瘤生长。

据介绍，过去五十年来，果糖的消费显著增加，主要是由于高果糖玉米糖浆作为甜味剂的广泛使用。有人提出，果糖通过作为燃料直接促进某些肿瘤的生长。

附：英文原文

Title: Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer

Author: Fowle-Grider, Ronald, Rowles, Joe L., Shen, Isabel, Wang, Yahui, Schwaiger-Haber, Michaela, Dunham, Alden J., Jayachandran, Kay, Inkman, Matthew, Zahner, Michael, Naser, Fuad J., Jackstadt, Madelyn M., Spalding, Jonathan L., Chiang, Sarah, McCommis, Kyle S., Dolle, Roland E., Kramer, Eva T., Zimmerman, Sarah M., Souroullas, George P., Finck, Brian N., Shriver, Leah P., Kaufman, Charles K., Schwarz, Julie K., Zhang, Jin, Patti, Gary J.

Issue&Volume: 2024-12-04

Abstract: Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener1. It has been proposed that fructose promotes the growth of some tumours directly by serving as a fuel2,3. Here we show that fructose supplementation enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer without causing weight gain or insulin resistance. The cancer cells themselves were unable to use fructose readily as a nutrient because they did not express ketohexokinase-C (KHK-C). Primary hepatocytes did express KHK-C, resulting in fructolysis and the excretion of a variety of lipid species, including lysophosphatidylcholines (LPCs). In co-culture experiments, hepatocyte-derived LPCs were consumed by cancer cells and used to generate phosphatidylcholines, the major phospholipid of cell membranes. In vivo, supplementation with high-fructose corn syrup increased several LPC species by more than sevenfold in the serum. Administration of LPCs to mice was sufficient to increase tumour growth. Pharmacological inhibition of ketohexokinase had no direct effect on cancer cells, but it decreased circulating LPC levels and prevented fructose-mediated tumour growth in vivo. These findings reveal that fructose supplementation increases circulating nutrients such as LPCs, which can enhance tumour growth through a cell non-autonomous mechanism.

DOI: 10.1038/s41586-024-08258-3

Source: https://www.nature.com/articles/s41586-024-08258-3