Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth^1,2,3,4,5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels^6,7,8, 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.

饮食干预可以改变肿瘤微环境中的代谢水平，从而可能影响癌细胞代谢，从而改变肿瘤生长^1,2,3,4,5。尽管热量限制 (CR) 和生酮饮食 (KD) 通常被认为可以通过降低血糖和胰岛素水平来限制肿瘤进展^6,7,8，但我们发现只有 CR 才能抑制小鼠中特定肿瘤同种异体移植物的生长，这表明其他机制有助于抑制肿瘤生长。CR 观察到的营养有效性变化是血浆和肿瘤中的脂质水平降低，而 KD 则没有。合成单不饱和脂肪酸的硬脂酰辅酶 A 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 还会损害肿瘤 SCD 活性，导致不饱和脂肪酸和饱和脂肪酸之间的不平衡，从而减缓肿瘤生长生长。通过高脂肪 CR 饮食增强癌细胞 SCD 表达或提高循环脂质水平，可以抵抗 CR 的影响。相比之下，尽管生酮饮食也会损害肿瘤 SCD 活性，但生酮饮食驱动的脂质可用性增加维持了肿瘤中不饱和脂肪酸与饱和脂肪酸的比例，并且改变生酮饮食脂肪组成以增加肿瘤饱和脂肪酸水平与肿瘤 SCD 活性降低相配合，从而减缓肿瘤的发生。肿瘤生长。这些数据表明，饮食引起的肿瘤脂肪酸去饱和活性与特定脂肪酸种类的可用性之间的不匹配决定了低血糖饮食是否损害肿瘤生长。