小柯机器人

瑞典卡洛琳卡学院Yihai Cao研究小组发现，棕色脂肪通过寒冷改变的整体代谢来抑制肿瘤。相关论文于2022年8月3日在线发表在《自然》杂志上。

研究人员表明，将肿瘤小鼠暴露在寒冷的条件下，可以明显地抑制各种类型的固体肿瘤的生长，包括临床上无法治疗的癌症，如胰腺癌。从机制上讲，寒冷诱导的棕色脂肪组织（BAT）激活大大降低了血糖，阻碍了癌细胞中基于糖酵解的代谢。移除BAT并在寒冷环境下喂食高糖饮食可恢复肿瘤生长，而Ucp1（BAT产热的关键媒介）的基因缺失会使寒冷触发的抗癌作用失效。在一项试验性的人体研究中，温和的冷暴露激活了健康人和一名癌症患者的大量BAT，并减轻了肿瘤组织中的葡萄糖摄取量。这些发现为癌症治疗提供了一个以前未曾描述过的概念和范式，且采用了一种简单而有效的方法。研究人员预计，通过任何其他方法，如单独或与其他抗癌疗法相结合的药物和设备，冷暴露和激活BAT，将为有效治疗各种癌症提供一种通用方法。

据悉，葡萄糖的摄取对癌症的糖酵解至关重要，并参与脂肪组织的非颤抖性产热。大多数癌症利用糖酵解来为其无限的生长、入侵和转移获取能量。寒冷和药物激活BAT的生热代谢会促进脂肪细胞的血糖摄取。然而，与BAT激活相关的整体代谢变化对肿瘤生长的功能影响尚不清楚。

附：英文原文

Title: Brown-fat-mediated tumour suppression by cold-altered global metabolism

Author: Seki, Takahiro, Yang, Yunlong, Sun, Xiaoting, Lim, Sharon, Xie, Sisi, Guo, Ziheng, Xiong, Wenjing, Kuroda, Masashi, Sakaue, Hiroshi, Hosaka, Kayoko, Jing, Xu, Yoshihara, Masahito, Qu, Lili, Li, Xin, Chen, Yuguo, Cao, Yihai

Issue&Volume: 2022-08-03

Abstract: Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1,2,3,4,5,6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1—the key mediator for BAT-thermogenesis—ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.

DOI: 10.1038/s41586-022-05030-3

Source: https://www.nature.com/articles/s41586-022-05030-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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