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Low glycaemic diets alter lipid metabolism to influence tumour growth

  • 1.

    Lien, E. C. & Vander Heiden, M. G. A framework for examining how diet impacts tumour metabolism. Nat. Rev. Cancer 19, 651–661 (2019).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 2.

    Sullivan, M. R. et al. Increased serine synthesis provides an advantage for tumors arising in tissues where serine levels are limiting. Cell Metab. 29, 1410–1421 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 3.

    Sullivan, M. R. et al. Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability. Elife 8, e44235 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 4.

    Maddocks, O. D. K. et al. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 544, 372–376 (2017).

    ADS 
    CAS 
    Article 

    Google Scholar
     

  • 5.

    Gao, X. et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature 572, 397–401 (2019).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 6.

    Kalaany, N. Y. & Sabatini, D. M. Tumours with PI3K activation are resistant to dietary restriction. Nature 458, 725–731 (2009).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 7.

    Hopkins, B. D. et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560, 499–503 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 8.

    Nencioni, A., Caffa, I., Cortellino, S. & Longo, V. D. Fasting and cancer: molecular mechanisms and clinical application. Nat. Rev. Cancer 18, 707–719 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 9.

    Danai, L. V. et al. Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature 558, 600–604 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 10.

    Gocheva, V. et al. Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival. Proc. Natl Acad. Sci. USA 114, E5625–E5634 (2017).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 11.

    Kennedy, A. R. et al. A high-fat, ketogenic diet induces a unique metabolic state in mice. Am. J. Physiol. Endocrinol. Metab. 292, E1724–E1739 (2007).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 12.

    Mukherjee, P., El-Abbadi, M. M., Kasperzyk, J. L., Ranes, M. K. & Seyfried, T. N. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br. J. Cancer 86, 1615–1621 (2002).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 13.

    Zhang, J. et al. Low ketolytic enzyme levels in tumors predict ketogenic diet responses in cancer cell lines in vitro and in vivo. J. Lipid Res. 59, 625–634 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 14.

    Hosios, A. M., Li, Z., Lien, E. C. & Vander Heiden, M. G. Preparation of lipid-stripped serum for the study of lipid metabolism in cell culture. Bio Protoc. 8, e2876 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 15.

    Peck, B. & Schulze, A. Lipid desaturation—the next step in targeting lipogenesis in cancer. FEBS J. 283, 2767–2778 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 16.

    Vriens, K. et al. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity. Nature 566, 403–406 (2019).

    ADS 
    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • 17.

    Kim, W. et al. Polyunsaturated fatty acid desaturation is a mechanism for glycolytic NAD+ recycling. Cell Metab. 29, 856–870 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 18.

    Sullivan, L. B. et al. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 162, 552–563 (2015).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 19.

    Birsoy, K. et al. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 162, 540–551 (2015).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 20.

    Titov, D. V. et al. Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio. Science 352, 231–235 (2016).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 21.

    Diehl, F. F., Lewis, C. A., Fiske, B. P. & Vander Heiden, M. G. Cellular redox state constrains serine synthesis and nucleotide production to impact cell proliferation. Nat. Metab. 1, 861–867 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 22.

    Piccolis, M. et al. Probing the global cellular responses to lipotoxicity caused by saturated fatty acids. Mol. Cell 74, 32–44 (2019).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 23.

    Mauvoisin, D. & Mounier, C. Hormonal and nutritional regulation of SCD1 gene expression. Biochimie 93, 78–86 (2011).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 24.

    Young, R. M. et al. Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress. Genes Dev. 27, 1115–1131 (2013).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 25.

    Ackerman, D. et al. Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep. 24, 2596–2605 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 26.

    Kamphorst, J. J. et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc. Natl Acad. Sci. USA 110, 8882–8887 (2013).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 27.

    Coulston, A. M. The role of dietary fats in plant-based diets. Am. J. Clin. Nutr. 70, 512S–515S (1999).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 28.

    Pascual, G. et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 541, 41–45 (2017).

    ADS 
    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 29.

    Siri-Tarino, P. W., Chiu, S., Bergeron, N. & Krauss, R. M. Saturated fats versus polyunsaturated fats versus carbohydrates for cardiovascular disease prevention and treatment. Annu. Rev. Nutr. 35, 517–543 (2015).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 30.

    Mayers, J. R. et al. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science 353, 1161–1165 (2016).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 31.

    Lewis, C. A. et al. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol. Cell 55, 253–263 (2014).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 32.

    Heinrich, P. et al. Correcting for natural isotope abundance and tracer impurity in MS-, MS/MS- and high-resolution-multiple-tracer-data from stable isotope labeling experiments with IsoCorrectoR. Sci. Rep. 8, 17910 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 33.

    Antoniewicz, M. R., Kelleher, J. K. & Stephanopoulos, G. Measuring deuterium enrichment of glucose hydrogen atoms by gas chromatography/mass spectrometry. Anal. Chem. 83, 3211–3216 (2011).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 34.

    Argus, J. P. et al. Development and application of FASA, a model for quantifying fatty acid metabolism using stable isotope labeling. Cell Rep. 25, 2919–2934 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 35.

    Vichai, V. & Kirtikara, K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc. 1, 1112–1116 (2006).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 36.

    Colditz, G. A. & Hankinson, S. E. The Nurses’ Health Study: lifestyle and health among women. Nat. Rev. Cancer 5, 388–396 (2005).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 37.

    Belanger, C. F., Hennekens, C. H., Rosner, B. & Speizer, F. E. The nurses’ health study. Am. J. Nurs. 78, 1039–1040 (1978).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 38.

    Health Professionals Follow-Up Study (Harvard T. H. Chan School of Public Health, 2020); https://sites.sph.harvard.edu/hpfs/

  • 39.

    Hu, F. B. et al. Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire. Am. J. Clin. Nutr. 69, 243–249 (1999).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 40.

    Feskanich, D. et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J. Am. Diet Assoc. 93, 790–796 (1993).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 41.

    Willett, W. C. et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am. J. Epidemiol. 122, 51–65 (1985).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 42.

    Rimm, E. B. et al. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am. J. Epidemiol. 135, 1114–1126 (1992).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 43.

    Willett, W. C. Nutritional Epidemiology (Oxford University Press, 2012).

  • 44.

    Yuan, C. et al. Validity of a dietary questionnaire assessed by comparison with multiple weighed dietary records or 24-hour recalls. Am. J. Epidemiol. 185, 570–584 (2017).

    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • 45.

    Yuan, C. et al. Relative validity of nutrient intakes assessed by questionnaire, 24-hour recalls, and diet records as compared with urinary recovery and plasma concentration biomarkers: findings for women. Am. J. Epidemiol. 187, 1051–1063 (2018).

    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 46.

    Halton, T. L., Liu, S., Manson, J. E. & Hu, F. B. Low-carbohydrate-diet score and risk of type 2 diabetes in women. Am. J. Clin. Nutr. 87, 339–346 (2008).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 47.

    Halton, T. L. et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N. Engl. J. Med. 355, 1991–2002 (2006).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 48.

    Liu, Y. et al. Plant-based and animal-based low-carbohydrate diets and risk of hepatocellular carcinoma among US men and women. Hepatology 73, 175–185 (2020).

    Article 
    CAS 

    Google Scholar
     

  • 49.

    Stampfer, M. J. et al. Test of the National Death Index. Am. J. Epidemiol. 119, 837–839 (1984).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 50.

    Rich-Edwards, J. W., Corsano, K. A. & Stampfer, M. J. Test of the National Death Index and Equifax Nationwide Death Search. Am. J. Epidemiol. 140, 1016–1019 (1994).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

  • 51.

    Colditz, G. A. et al. Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am. J. Epidemiol. 123, 894–900 (1986).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar
     

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