Low glycaemic diets alter lipid metabolism to influence tumour growth

Evan C. Lien, Anna M. Westermark, Yin Zhang, Chen Yuan, Zhaoqi Li, Allison N. Lau, Kiera M. Sapp, Brian M. Wolpin and Matthew G. Vander Heiden ()
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Evan C. Lien: Massachusetts Institute of Technology
Anna M. Westermark: Massachusetts Institute of Technology
Yin Zhang: Dana-Farber Cancer Institute
Chen Yuan: Dana-Farber Cancer Institute
Zhaoqi Li: Massachusetts Institute of Technology
Allison N. Lau: Massachusetts Institute of Technology
Kiera M. Sapp: Massachusetts Institute of Technology
Brian M. Wolpin: Dana-Farber Cancer Institute
Matthew G. Vander Heiden: Massachusetts Institute of Technology

Nature, 2021, vol. 599, issue 7884, 302-307

Abstract: Abstract Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth1–5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels6–8, 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.

Date: 2021
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DOI: 10.1038/s41586-021-04049-2

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