Astrocyte Lipid Homeostasis is Regulated by Glutamate

• Author / Creator

  Rubio Atonal, Luis Fernando

• Astrocytes can store excess fatty acids in lipid droplets to avoid lipotoxicity. Fatty acids can be released from lipid droplets and catabolized to generate energy in the mitochondria. We previously found reduced astrocytic lipid droplets and increased transport of fatty acids into the mitochondria in response to glutamate, the major excitatory neurotransmitter in the brain. Whether glutamate affects fatty acid catabolism and how glutamate regulates lipid droplet homeostasis in astrocytes is unknown. Here, we show that astrocytes use glutamate directly as fuel for increased oxidative phosphorylation while decreasing their use of glycolysis for ATP production. Importantly, glutamate had no effect on fatty acid catabolism in mitochondria. Instead, increased fatty acid transport is likely used for mitochondrial maintenance as we found decreased reactive oxygen species with a concomitant increase in mitochondrial mass upon glutamate treatment. Consistent with healthier mitochondria, we observed that glutamate increased AMPK phosphorylation and supressed the induction of autophagy, which probably reduces the lipid flux into lipid droplets. Altogether, this study reveals how exogenous application of glutamate, a major excitatory neurotransmitter in the brain, regulates fatty acid homeostasis in astrocytes.

• Subjects / Keywords

  • astrocyte
  • lipid metabolism
  • glutamate
  • mitochondria
  • metabolism

• Graduation date

  Fall 2024

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-gazv-9k79

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.