Supplementation of Medium-Chain Triglycerides Combined with Docosahexaenoic Acid Inhibits Amyloid Beta Protein Deposition by Improving Brain Glucose Metabolism in APP/PS1 Mice

Nutrients. 2023 Oct 1;15(19):4244. doi: 10.3390/nu15194244.

Abstract

The deterioration of brain glucose metabolism predates the clinical onset of Alzheimer's disease (AD). Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively improve brain glucose metabolism and decrease the expression of AD-related proteins. However, the effects of the combined intervention are unclear. The present study explored the effects of the supplementation of MCTs combined with DHA in improving brain glucose metabolism and decreasing AD-related protein expression levels in APP/PS1 mice. The mice were assigned into four dietary treatment groups: the control group, MCTs group, DHA group, and MCTs + DHA group. The corresponding diet of the respective groups was fed to mice from the age of 3 to 11 months. The results showed that the supplementation of MCTs combined with DHA could increase serum octanoic acid (C8:0), decanoic acid (C10:0), DHA, and β-hydroxybutyrate (β-HB) levels; improve glucose metabolism; and reduce nerve cell apoptosis in the brain. Moreover, it also aided with decreasing the expression levels of amyloid beta protein (Aβ), amyloid precursor protein (APP), β-site APP cleaving enzyme-1 (BACE1), and presenilin-1 (PS1) in the brain. Furthermore, the supplementation of MCTs + DHA was significantly more beneficial than that of MCTs or DHA alone. In conclusion, the supplementation of MCTs combined with DHA could improve energy metabolism in the brain of APP/PS1 mice, thus decreasing nerve cell apoptosis and inhibiting the expression of Aβ.

Keywords: 18F-FDG-PET-CT; APP/PS1 mouse; Alzheimer’s disease; amyloid beta protein; docosahexaenoic acid; glucose metabolism; medium-chain triglycerides.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides* / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / metabolism
  • Brain / metabolism
  • Dietary Supplements
  • Disease Models, Animal
  • Docosahexaenoic Acids / metabolism
  • Mice
  • Mice, Transgenic
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Triglycerides / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Amyloid Precursor Protein Secretases
  • Docosahexaenoic Acids
  • Presenilin-1
  • Aspartic Acid Endopeptidases
  • Triglycerides