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Astrocytes in stress accumulate lipid droplets

Smolič, Tina, Tavčar, Petra, Horvat, Anemari, Černe, Urška, Halužan Vasle, Ana, Tratnjek, Larisa, Kreft, Mateja Erdani, Scholz, Nicole, Matis, Maja, Petan, Toni, Zorec, Robert, Vardjan, Nina·2021·Glia
DOI 10.1002/glia.23978PMC PMC8248329
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Abstract

When the brain is in a pathological state, the content of lipid droplets (LDs), the lipid storage organelles, is increased, particularly in glial cells, but rarely in neurons. The biology and mechanisms leading to LD accumulation in astrocytes, glial cells with key homeostatic functions, are poorly understood. We imaged fluorescently labeled LDs by microscopy in isolated and brain tissue rat astrocytes and in glia‐like cells in Drosophila brain to determine the (sub)cellular localization, mobility, and content of LDs under various stress conditions characteristic for brain pathologies. LDs exhibited confined mobility proximal to mitochondria and endoplasmic reticulum that was attenuated by metabolic stress and by increased intracellular Ca 2+ , likely to enhance the LD–organelle interaction imaged by electron microscopy. When de novo biogenesis of LDs was attenuated by inhibition of DGAT1 and DGAT2 enzymes, the astrocyte cell number was reduced by ~40%, suggesting that in astrocytes LD turnover is important for cell survival and/or proliferative cycle. Exposure to noradrenaline, a brain stress response system neuromodulator, and metabolic and hypoxic stress strongly facilitated LD accumulation in astrocytes. The observed response of stressed astrocytes may be viewed as a support for energy provision, but also to be neuroprotective against the stress‐induced lipotoxicity.

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  • LDs may act as indirect markers of oxidative stress, as oxidized lipids are transferred from neurons to astrocytes through neuron-astrocyte metabolic coupling mechanisms.

    “Emerging evidence further suggests that LDs may act as indirect markers of oxidative stress, as oxidized lipids are transferred from neurons to astrocytes through neuron–astrocyte metabolic coupling mechanisms (Liu and Zhang 2014; Smolič et al. 2021).”

    From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Smolič et al. 2021

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Metadata

Authors
Smolič, T., Tavčar, P., Horvat, A., Černe, U., Halužan Vasle, A., Tratnjek, L., Kreft, M. E., Scholz, N., Matis, M., Petan, T., Zorec, R., & Vardjan, N.
Affiliations
  • Laboratory of Neuroendocrinology‐Molecular Cell Physiology, Faculty of Medicine Institute of Pathophysiology, University of Ljubljana Ljubljana Slovenia
  • Faculty of Medicine Institute of Cell Biology, University of Ljubljana Ljubljana Slovenia
  • Division of General Biochemistry, Medical Faculty Rudolf Schönheimer Institute of Biochemistry, Leipzig University Leipzig Germany
  • Medical Faculty Institute of Cell Biology, University of Münster Münster Germany
  • Department of Molecular and Biomedical Sciences Jožef Stefan Institute Ljubljana Slovenia
ORCID
Venue
Glia
Publisher
Wiley
Published
2021-02-20
Volume
69
Issue
6
Pages
1540-1562
ISSN
  • 0894-1491
  • 1098-1136
DOI
10.1002/glia.23978
PMC
PMC8248329
Cited by
127
References
9
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Funders
  • European Cooperation in Science and Technology (CM1207, CA18133, CA19105)
  • Deutsche Forschungsgemeinschaft (EXC‐1003, FOR 2149/P01 (SCHO 1791/1‐2), CRC 1423, project number 421152132, subproject B06)
  • Javna Agencija za Raziskovalno Dejavnost RS (P1‐0207, J7‐1818, P3‐0310, J3‐2523, BI‐DE/18‐19‐015, J3‐9266, J7‐2594)

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