Effects of plant-based versus marine-based omega-3 fatty acids and sucrose on brain and liver fatty acids in a mouse model of chemotherapy

Nutr Neurosci. 2022 Dec;25(12):2650-2658. doi: 10.1080/1028415X.2021.1998296. Epub 2021 Nov 12.

Abstract

Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

Keywords: ALA; DHA; EPA; Omega-3 fatty acids; alpha-linolenic acid; brain; chemotherapy; doxorubicin.

MeSH terms

  • Animals
  • Biomarkers
  • Brain
  • Brain-Derived Neurotrophic Factor
  • Disease Models, Animal
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids*
  • Fatty Acids, Omega-3*
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Sucrose

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Sucrose