Astrocytes in stress accumulate lipid droplets

Smolič, Tina (author), Tavčar Verdev, Petra (author), Horvat, Anemari (author), Černe, Urška (author), Halužan Vasle, Ana (author), Tratnjek, Larisa (author), Erdani-Kreft, Mateja (author), Scholz, Nicole (author), Matis, Maja (author), Petan, Toni (author), Zorec, Robert (author), Vardjan, Nina (author)

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.

• Language: English
• Keywords: astrocytes, stress stimuli, metabolism, adrenergic receptors, lipid droplets, metabolic stress, hypoxic stress, noradrenaline
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: Str. 1540-1562
• Numbering: Vol. 69, iss. 6
• PID: 20.500.12556/RUL-144756
• UDC: 616-092
• ISSN on article: 0894-1491
• DOI: 10.1002/glia.23978
• COBISS.SI-ID: 52537347
• Publication date in RUL: 10.03.2023

Record is a part of a journal

• Title: Glia
• Shortened title: Glia
• Publisher: Wiley
• ISSN: 0894-1491
• COBISS.SI-ID: 14837721

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: astrociti, stresni dražljaji, presnova