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Open AccessArticle

Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation

1
Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, MI 48309, USA
2
Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA
3
Department of Pharmacology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Alessandro Tozzi
Cells 2021, 10(2), 198; https://doi.org/10.3390/cells10020198
Received: 2 December 2020 / Revised: 12 January 2021 / Accepted: 15 January 2021 / Published: 20 January 2021
(This article belongs to the Special Issue Microglia in Aging and Neurodegenerative Diseases)
Microglia become increasingly dysfunctional with aging and contribute to the onset of neurodegenerative disease (NDs) through defective phagocytosis, attenuated cholesterol efflux, and excessive secretion of pro-inflammatory cytokines. Dysfunctional microglia also accumulate lipid droplets (LDs); however, the mechanism underlying increased LD load is unknown. We have previously shown that microglia lacking lipoprotein lipase (LPL KD) are polarized to a pro-inflammatory state and have impaired lipid uptake and reduced fatty acid oxidation (FAO). Here, we also show that LPL KD microglia show excessive accumulation of LD-like structures. Moreover, LPL KD microglia display a pro-inflammatory lipidomic profile, increased cholesterol ester (CE) content, and reduced cholesterol efflux at baseline. We also show reduced expression of genes within the canonical cholesterol efflux pathway. Importantly, PPAR agonists (rosiglitazone and bezafibrate) rescued the LD-associated phenotype in LPL KD microglia. These data suggest that microglial-LPL is associated with lipid uptake, which may drive PPAR signaling and cholesterol efflux to prevent inflammatory lipid distribution and LD accumulation. Moreover, PPAR agonists can reverse LD accumulation, and therefore may be beneficial in aging and in the treatment of NDs. View Full-Text
Keywords: lipoprotein lipase; PPAR agonists; microglia; neurodegenerative disease; lipid droplet lipoprotein lipase; PPAR agonists; microglia; neurodegenerative disease; lipid droplet
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MDPI and ACS Style

Loving, B.A.; Tang, M.; Neal, M.C.; Gorkhali, S.; Murphy, R.; Eckel, R.H.; Bruce, K.D. Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation. Cells 2021, 10, 198. https://doi.org/10.3390/cells10020198

AMA Style

Loving BA, Tang M, Neal MC, Gorkhali S, Murphy R, Eckel RH, Bruce KD. Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation. Cells. 2021; 10(2):198. https://doi.org/10.3390/cells10020198

Chicago/Turabian Style

Loving, Bailey A.; Tang, Maoping; Neal, Mikaela C.; Gorkhali, Sachi; Murphy, Robert; Eckel, Robert H.; Bruce, Kimberley D. 2021. "Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation" Cells 10, no. 2: 198. https://doi.org/10.3390/cells10020198

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