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Low glycaemic diets alter lipid metabolism to influence tumour growth

Author

Listed:
  • Evan C. Lien

    (Massachusetts Institute of Technology)

  • Anna M. Westermark

    (Massachusetts Institute of Technology)

  • Yin Zhang

    (Dana-Farber Cancer Institute
    Harvard T. H. Chan School of Public Health)

  • Chen Yuan

    (Dana-Farber Cancer Institute)

  • Zhaoqi Li

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Allison N. Lau

    (Massachusetts Institute of Technology)

  • Kiera M. Sapp

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Brian M. Wolpin

    (Dana-Farber Cancer Institute)

  • Matthew G. Vander Heiden

    (Massachusetts Institute of Technology
    Dana-Farber Cancer Institute
    Massachusetts Institute of Technology)

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.

Suggested Citation

  • 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, 2021. "Low glycaemic diets alter lipid metabolism to influence tumour growth," Nature, Nature, vol. 599(7884), pages 302-307, November.
  • Handle: RePEc:nat:nature:v:599:y:2021:i:7884:d:10.1038_s41586-021-04049-2
    DOI: 10.1038/s41586-021-04049-2
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    Cited by:

    1. Ziheng Chen & I-Lin Ho & Melinda Soeung & Er-Yen Yen & Jintan Liu & Liang Yan & Johnathon L. Rose & Sanjana Srinivasan & Shan Jiang & Q. Edward Chang & Ningping Feng & Jason P. Gay & Qi Wang & Jing Wa, 2023. "Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Yanjie Tan & Zhenzhou Huang & Yi Jin & Jiaying Wang & Hongjun Fan & Yangyang Liu & Liang Zhang & Yue Wu & Peiwei Liu & Tianliang Li & Jie Ran & He Tian & Sin Man Lam & Min Liu & Jun Zhou & Yunfan Yang, 2024. "Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Niranjan Venkateswaran & Roy Garcia & M. Carmen Lafita-Navarro & Yi-Heng Hao & Lizbeth Perez-Castro & Pedro A. S. Nogueira & Ashley Solmonson & Ilgen Mender & Jessica A. Kilgore & Shun Fang & Isabella, 2024. "Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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