Nature:生酮饮食不能抗癌,但限制热量可以,切断脂质供应,抑制肿瘤生长

2022-01-05 “生物世界”公众号 “生物世界”公众号

生酮饮食是一种脂肪高比例、碳水化合物低比例,蛋白质和其他营养素合适的配方饮食。当人们进行生酮饮食时,身体会代谢产生更多的酮体(包括乙酰乙酸、β-羟丁酸和丙酮),以用作能量来源。

生酮饮食(ketogenic-diet,KD)是一种脂肪高比例、碳水化合物低比例,蛋白质和其他营养素合适的配方饮食。当人们进行生酮饮食时,身体会代谢产生更多的酮体(包括乙酰乙酸、β-羟丁酸和丙酮),以用作能量来源。

热量限制(caloric restriction,CR)是指在提供充分的营养成分如必需氨基酸、维生素等,保证不发生营养不良的情况下,限制每日摄取的总热量,将总热量减少25-50%。有研究表明,热量限制不但能延缓肿瘤生长,还能延长实验动物的寿命。

这两种饮食方式,都属于低血糖指数饮食,因为这种饮食方式不会在进食后迅速提高血糖水平。而低血糖指数饮食能够将血糖水平和胰岛素水平控制在最低,这与一些动物模型中的肿瘤生长受到抑制有关,因此低血糖指数饮食被认为能够抑制肿瘤生长,但与这类饮食相关的其他代谢变化是否会影响肿瘤生长却并不清楚。

对于大多数癌症患者来说,是不能进行长期进行低血糖饮食的,因为这样会导致他们体重减轻和肌肉质量降低,不利于疾病治疗。但生酮饮食和定期模拟禁食已经在癌症治疗的临床试验中进行了。这些饮食调节方式对于癌症究竟有何种效果呢?

2021年10月20日,麻省理工学院的 Matthew Vander Heiden 等人在 Nature 发表了题为:Low glycaemic diets alter lipid metabolism to influence tumour growth 的研究论文。

这项研究通过胰腺癌小鼠模型发现,只有热量限制能够抑制肿瘤生长,而生酮饮食则不行。

并进一步揭示了背后的机制:热量限制既降低了血浆和肿瘤中的血脂水平,又降低了硬脂酰辅酶A去饱和酶(SCD)活性,导致癌细胞既无法从饮食中获取脂质,又难以自己生产,从而导致肿瘤生长受限。而生酮饮食虽然也降低了SCD活性,但却增加了血脂水平,因此癌细胞可以通过饮食获取足够的脂质来生长分裂。

利用癌细胞的这一特点,可以通过抑制SCD的活性,来抑制肿瘤生长,这可能代表了癌症治疗的一个新方向。

癌细胞会消耗大量葡萄糖,因此人们认为生酮饮食或热量限制可能通过减少癌细胞可用的葡萄糖量来减缓肿瘤生长。

研究团队使用胰腺癌小鼠模型对这两种饮食方式进行了研究,结果发现,只有热量限制能够抑制肿瘤生长,因此,研究团队猜测这两种饮食方式对血糖水平的降低,在抑制肿瘤生长中发挥的作用并不大。

图a:热量限制饮食显着抑制了肿瘤生长;图b:生酮饮食未能显着抑制肿瘤生长

研究团队进行了进一步分析,发现这两种饮食方式的不同之处:热量限制既降低了血糖水平,又降低了血脂水平,而生酮饮食只降低了血糖水平,却提高了血脂水平。

缺少脂质会限制肿瘤生长,因为快速分裂的癌细胞需要脂质来构建细胞膜,当组织中缺乏脂质时,细胞可以自己制造,这个制造过程需要保持饱和脂肪酸与不饱和脂肪酸的平衡,这种平衡是由硬脂酰辅酶A去饱和酶(SCD)调控的,这种酶负责将饱和脂肪酸转化为不饱和脂肪酸。

而热量限制不但降低了血浆和肿瘤中的血脂水平,还降低了硬脂酰辅酶A去饱和酶(SCD)的活性,打破了饱和脂肪酸与不饱和脂肪酸之间的平衡,进一步削弱了肿瘤的生存环境。

虽然生酮饮食也会破坏硬脂酰辅酶A去饱和酶(SCD)的活性,但生酮饮食会增加血脂,从而将饱和脂肪酸与不饱和脂肪的比例维持在对肿瘤生长有利的水平。

图a:限制热量带来的代谢变化能够抑制肿瘤生长;图b:生酮饮食带来的代谢变化不能抑制肿瘤生长

除了小鼠实验外,研究团队还分析了1165名胰腺癌患者的饮食模式与生存时间之间的关系,初步发现显示,脂肪含量高、碳水化合物含量低的饮食可能与生存时间更长有关,但也与具体的脂肪摄入类型有关。

尽管这项研究显示热量限制能够抑制肿瘤生长,但作者也指出,这种饮食方式并不一定适合所有的癌症患者,因为热量限制这种饮食模式难以坚持,如果能坚持则会导致体重减轻,对于癌症患者来说,体重减轻可能会限制治疗方案的选择。

不过这项研究揭示了肿瘤对不饱和脂肪酸的依赖,在血脂水平低的情况下,抑制硬脂酰辅酶A去饱和酶(SCD)的活性,能够切断癌细胞产生不饱和脂肪酸的能力,从而抑制肿瘤生长。

作者认为,进一步研究饮食会如何影响干预肿瘤生长的代谢变化,或能指导如何在已有的癌症治疗策略中加入模拟这类作用的饮食或疗法。

第一作者 Evan C. Lien(左),通讯作者 Matthew Vander Heiden(右)

原始出处:

Lien, E.C., Westermark, A.M., Zhang, Y. et al. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature 599, 302–307 (2021). https://doi.org/10.1038/s41586-021-04049-2.

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    2022-12-14 liye789132251
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    2022-01-05 柳叶一刀

    学习了

    0

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    2022-01-05 ms9000001014338978

    已学

    0

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    2022-01-05 ms6000000830107622

    是一种脂肪高比例、碳水化合物低比例,蛋白质和其他营养素合适的配方饮食

    0

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    2022-01-05 医鸣惊人

    认真学习了

    0

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