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Article

Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation

1
Department of Physiology, University of Kentucky, 800 Rose Street, Rm: MS-609, Lexington, KY 40536, USA
2
Sanders-Brown Center on Aging, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(2), 182; https://doi.org/10.3390/cells8020182
Received: 30 January 2019 / Revised: 15 February 2019 / Accepted: 19 February 2019 / Published: 20 February 2019
Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (APOE) and neurodegeneration. The E4 allele of APOE (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD). Since both E4 carriers and individuals with AD exhibit a state of cerebral lipid dyshomeostasis, we hypothesized that APOE may play a role in regulating LD metabolism. We found that astrocytes expressing E4 accumulate significantly more and smaller LDs compared to E3 astrocytes. Accordingly, expression of perilipin-2, an essential LD protein component, was higher in E4 astrocytes. We then probed fatty acid (FA) metabolism and found E4 astrocytes to exhibit decreased uptake of palmitate, and decreased oxidation of exogenously supplied oleate and palmitate. We then measured oxygen consumption rate, and found E4 astrocytes to consume more oxygen for endogenous FA oxidation and accumulate more LD-derived metabolites due to incomplete oxidation. Lastly, we found that E4 astrocytes are more sensitive to carnitine palmitoyltransferase-1 inhibition than E3 astrocytes. These findings offer the potential for further studies investigating the link between astrocyte lipid storage, utilization, and neurodegenerative disease as a function of APOE genotype. View Full-Text
Keywords: APOE; astrocytes; lipid droplets; lipid metabolism; AD; PLIN-2; fatty acid oxidation APOE; astrocytes; lipid droplets; lipid metabolism; AD; PLIN-2; fatty acid oxidation
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MDPI and ACS Style

Farmer, B.C.; Kluemper, J.; Johnson, L.A. Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation. Cells 2019, 8, 182. https://doi.org/10.3390/cells8020182

AMA Style

Farmer BC, Kluemper J, Johnson LA. Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation. Cells. 2019; 8(2):182. https://doi.org/10.3390/cells8020182

Chicago/Turabian Style

Farmer, Brandon C., Jude Kluemper, and Lance A. Johnson 2019. "Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation" Cells 8, no. 2: 182. https://doi.org/10.3390/cells8020182

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