Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation
Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (<i>APOE</i>) and neurodegeneration. The E4 allele of <i>APOE</i> (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD)...
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MDPI AG
2019-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/2/182 |
| _version_ | 1797727505117872128 |
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| author | Brandon C. Farmer Jude Kluemper Lance A. Johnson |
| author_facet | Brandon C. Farmer Jude Kluemper Lance A. Johnson |
| author_sort | Brandon C. Farmer |
| collection | DOAJ |
| description | Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (<i>APOE</i>) and neurodegeneration. The E4 allele of <i>APOE</i> (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 <i>APOE</i> 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 <i>APOE</i> genotype. |
| first_indexed | 2024-03-12T11:00:41Z |
| format | Article |
| id | doaj.art-8efe509925e240aea0939defda624574 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T11:00:41Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8efe509925e240aea0939defda6245742023-09-02T05:48:17ZengMDPI AGCells2073-44092019-02-018218210.3390/cells8020182cells8020182Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet FormationBrandon C. Farmer0Jude Kluemper1Lance A. Johnson2Department of Physiology, University of Kentucky, 800 Rose Street, Rm: MS-609, Lexington, KY 40536, USADepartment of Physiology, University of Kentucky, 800 Rose Street, Rm: MS-609, Lexington, KY 40536, USADepartment of Physiology, University of Kentucky, 800 Rose Street, Rm: MS-609, Lexington, KY 40536, USALipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (<i>APOE</i>) and neurodegeneration. The E4 allele of <i>APOE</i> (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 <i>APOE</i> 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 <i>APOE</i> genotype.https://www.mdpi.com/2073-4409/8/2/182APOEastrocyteslipid dropletslipid metabolismADPLIN-2fatty acid oxidation |
| spellingShingle | Brandon C. Farmer Jude Kluemper Lance A. Johnson Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation Cells APOE astrocytes lipid droplets lipid metabolism AD PLIN-2 fatty acid oxidation |
| title | Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation |
| title_full | Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation |
| title_fullStr | Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation |
| title_full_unstemmed | Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation |
| title_short | Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism and Lipid Droplet Formation |
| title_sort | apolipoprotein e4 alters astrocyte fatty acid metabolism and lipid droplet formation |
| topic | APOE astrocytes lipid droplets lipid metabolism AD PLIN-2 fatty acid oxidation |
| url | https://www.mdpi.com/2073-4409/8/2/182 |
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