Open AccessLow glycaemic diets alter lipid metabolism to influence tumour growth
Author(s) -
Evan C. Lien,
Anna M. Westermark,
Yin Zhang,
Chen Yuan,
Zhaoqi Li,
Allison N. Lau,
Kiera M. Sapp,
Brian M. Wolpin,
Matthew G. Vander Heiden
Publication year - 2021
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-021-04049-2
Subject(s) - lipid metabolism , fatty acid , endocrinology , medicine , metabolism , downregulation and upregulation , fatty acid synthesis , metabolite , biology , saturated fatty acid , cell growth , fatty acid metabolism , chemistry , linoleic acid , biochemistry , gene
Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth 1-5 . Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels 6-8 , 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.