小柯机器人

美国麻省理工学院Matthew G. Vander Heiden课题组发现，低血糖饮食改变脂质代谢来影响肿瘤的生长。2021年10月20日，国际知名学术期刊《自然》在线发表了这一成果。

虽然热量限制（CR）和生酮饮食（KD）通常被认为是通过降低血糖和胰岛素水平来限制肿瘤的发展，但研究人员发现只有CR能抑制小鼠体内特定肿瘤移植体的生长，这表明其他机制有助于抑制肿瘤的生长。CR中观察到的营养供应变化是血浆和肿瘤中的脂质水平降低。合成单不饱和脂肪酸的硬脂酰-CoA去饱和酶（SCD）的上调是癌细胞在脂质耗尽的环境中增殖所必需的，CR也会损害肿瘤SCD的活性，导致不饱和脂肪酸和饱和脂肪酸之间的不平衡，从而减缓肿瘤的生长。通过较高脂肪的CR饮食，强制癌细胞SCD的表达或提高循环脂质水平，使其对CR的影响产生抵抗。

相比之下，尽管KD也损害了肿瘤SCD的活性，但KD驱动的脂质供应增加维持了肿瘤中不饱和脂肪酸的比例，并且改变KD脂肪组成来提高肿瘤饱和脂肪酸水平能够与降低肿瘤SCD的活性共同来减缓肿瘤生长速度。这些数据表明，饮食引起的肿瘤脂肪酸去饱和化活性和特定脂肪酸种类可用性之间的不匹配决定了低血糖饮食是否会损害肿瘤生长。

据悉，饮食干预可以改变肿瘤微环境中的代谢物水平，进而影响癌细胞的代谢，改变肿瘤的生长。

附：英文原文

Title: Low glycaemic diets alter lipid metabolism to influence tumour growth

Author: Lien, Evan C., Westermark, Anna M., Zhang, Yin, Yuan, Chen, Li, Zhaoqi, Lau, Allison N., Sapp, Kiera M., Wolpin, Brian M., Vander Heiden, Matthew G.

Issue&Volume: 2021-10-20

Abstract: Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth1,2,3,4,5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels6,7,8, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting that other mechanisms contribute to tumour growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumours. Upregulation of stearoyl-CoA desaturase (SCD), which synthesises monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumour SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumour growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumour SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumours, and changing the KD fat composition to increase tumour saturated fatty acid levels cooperates with decreased tumour SCD activity to slow tumour growth. These data suggest that diet-induced mismatches between tumour fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycaemic diets impair tumour growth.

DOI: 10.1038/s41586-021-04049-2

Source: https://www.nature.com/articles/s41586-021-04049-2

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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