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Astrocytes in stress accumulate lipid droplets
Author(s) -
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
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23978
Subject(s) - astrocyte , lipid droplet , microbiology and biotechnology , biology , endoplasmic reticulum , organelle , mitochondrion , lipotoxicity , neuroglia , lipid metabolism , neuroprotection , intracellular , unfolded protein response , neuroscience , biochemistry , central nervous system , endocrinology , insulin resistance , insulin
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.