Journal Article

Low glycaemic diets alter lipid metabolism to influence tumour growth

Li, Zhaoqi, Lau, Allison N., Wolpin, Brian M., Zhang, Yin, Lien, Evan C., Westermark, Anna M., Sapp, Kiera M., Vander Heiden, Matthew G., Yuan, Chen

2021

Overview

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. Lien et al. show that low glycemic diets can reduce tumour growth by deregulating lipid metabolism.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/106 / 13/51 / 631/45/287/1183 / 631/45/320 / 631/67/2327 / 64/60 / 82/29 / 82/58 / 96/1 / Adenocarcinoma of Lung - metabolism / Adenocarcinoma of Lung - pathology / Allografts / Animals / Availability / Blood glucose / Blood Glucose - metabolism / Body fat / Caloric Restriction / Cancer / Carcinoma, Pancreatic Ductal - metabolism / Carcinoma, Pancreatic Ductal - pathology / Cell growth / Cell Line, Tumor / Cell Proliferation / Desaturase / Desaturation / Dextrose / Diet / Diet therapy / Diet, Carbohydrate-Restricted / Diet, Ketogenic / Dietary restrictions / Extracellular Fluid - chemistry / Fatty acids / Fatty Acids - metabolism / Fatty Acids, Unsaturated - metabolism / Female / Glucose / Health aspects / High fat diet / Humanities and Social Sciences / Insulin / Ketogenesis / Lipid metabolism / Lipid Metabolism - drug effects / Lipids / Low carbohydrate diet / Male / Metabolism / Metabolites / Mice / Mice, Inbred C57BL / Microenvironments / multidisciplinary / Neoplasm Transplantation / Neoplasms - metabolism / Neoplasms - pathology / Nutrient availability / Nutrient deficiency / Nutrients - analysis / Nutrients - blood / Physiological aspects / Plasma / Ratios / Science / Science (multidisciplinary) / Stearoyl-CoA desaturase / Stearoyl-CoA Desaturase - metabolism / Tumor microenvironment / Tumor Microenvironment - drug effects / Tumors