The Brain on a High Fat Diet: The Effects of Beta‐Hydroxybutyrate on Astrocytes

Abstract

Astrocytes are brain cells that store and transport energy to neurons in the form of glucose. When glucose levels are low or absent, fat is metabolized and ketone bodies are created as an alternative energy source. In recent years, alternative dieting strategies such as low carbohydrate/high fat and intermittent fasting have become popular. Interestingly, these diets have shown therapeutic potential in treatment of diseases including Alzheimer's disease and epilepsy. However, it is unknown how astrocytes are affected by these diets. Ketogenesis results in the production of 3 ketone bodies: beta‐hydroxybutyrate (βHB), acetone and acetoacetate. Previous studies have shown that βHB levels increase significantly in the brain under ketogenic conditions. Thus, we chose to focus on how replacement of glucose with βHB impacts number and morphology of C6 astrocytic cells. Four experimental groups were tested: No Glucose/No βHB, 25mM Glucose (control), 1mM βHB, and 25mM βHB. Following treatment, cell morphology was visualized via actin immunohistochemistry (IHC) and nuclei were labeled using diamindino‐2‐phenylindole (DAPI). Quantification of the DAPI staining revealed a significant decrease in cell number in the No Glucose/No βHB, 1mM βHB and 25mM βHB groups compared to the 25mM Glucose control. Cells in the No Glucose/No βHB and 1mM βHB groups exhibited a rounded shape distinct from the 25mM Glucose and 25mM βHB groups. While previous studies have shown positive effects of a ketone‐rich diet, these results suggest that astrocyte health may be impaired when βHB is substituted for glucose.This work was supported by the Westfield State University Research Grant.