Low-glycemic diets that decrease circulating lipids limit tumor growth.

  • Major Finding: Low-glycemic diets that decrease circulating lipids limit tumor growth.

  • Concept: Low lipid conditions cause imbalance of unsaturated and saturated fatty acids in tumors.

  • Impact: This study highlights the impact of dietary interventions on tumor progression.

Low-glycemic diets have been thought to limit tumor progression by lowering blood glucose and insulin levels, but whether other nutrients also contribute is unknown. To address this, Lien and colleagues exposed tumor-bearing mice to control diet, caloric restriction (CR), or ketogenic diet (KD). Mice with CR had impaired tumor growth while mice with KD did not; however, both diets lowered blood glucose levels, indicating that there may be alternative mechanisms in which low-glycemic diets restrict tumor growth. Metabolite levels in plasma and tumor interstitial fluid from mice exposed to restricted diets were measured by gas chromatography–mass spectrometry analysis and indicated a reduction in fatty acid levels in CR mice. In lipid-depleted conditions, cells must increase Stearoyl-CoA desaturase (SCD) activity, an enzyme that converts saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) to maintain appropriate ratios of MUFAs and SFAs in cells and prevent SFA accumulation. Tumors from both CR and KD mice had reduced SCD activity with only tumors from CR mice showing decreased MUFA levels and MUFA/SFA ratio. As CR limits total lipid availability while KD still retains MUFA, further experiments indicated that CR caused imbalance of unsaturated to saturated fatty acids and subsequently restricted tumor growth. Cancer cells engineered to express SCD partially rescued CR-mediated inhibition of tumor growth, and a high-fat caloric restriction diet increased systemic lipid availability, rescuing CR-mediated restricted tumor growth and loss of SCD activity. Consistent with in vitro findings that SFA accumulation can be toxic to cells, a palm oil–based KD that contains high SFA increased SFAs within tumors and inhibited tumor growth, which was rescued by exogenous SCD. These findings argue that reduced SCD expression associated with low insulin in low-glycemic diets can result in an imbalance of saturated and unsaturated fatty acids to slow tumor growth, but this depends on how diet affects lipid availability in tumors, suggesting that further investigation of these dietary interventions in patients with cancer may be warranted.

Lien EC, Westermark AM, Zhang Y, Yuan C, Li Z, Lau AN, et al. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature 2021 Oct 20 [Epub ahead of print].

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