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Review
. 2021 Dec 23;11(1):22.
doi: 10.3390/antiox11010022.

Pathophysiology of Lipid Droplets in Neuroglia

Tina Smolič  1   2 , Robert Zorec  1   2 , Nina Vardjan  1   2
Affiliations
Review

Pathophysiology of Lipid Droplets in Neuroglia

Tina Smolič et al. Antioxidants (Basel). .

Abstract

In recent years, increasing evidence regarding the functional importance of lipid droplets (LDs), cytoplasmic storage organelles in the central nervous system (CNS), has emerged. Although not abundantly present in the CNS under normal conditions in adulthood, LDs accumulate in the CNS during development and aging, as well as in some neurologic disorders. LDs are actively involved in cellular lipid turnover and stress response. By regulating the storage of excess fatty acids, cholesterol, and ceramides in addition to their subsequent release in response to cell needs and/or environmental stressors, LDs are involved in energy production, in the synthesis of membranes and signaling molecules, and in the protection of cells against lipotoxicity and free radicals. Accumulation of LDs in the CNS appears predominantly in neuroglia (astrocytes, microglia, oligodendrocytes, ependymal cells), which provide trophic, metabolic, and immune support to neuronal networks. Here we review the most recent findings on the characteristics and functions of LDs in neuroglia, focusing on astrocytes, the key homeostasis-providing cells in the CNS. We discuss the molecular mechanisms affecting LD turnover in neuroglia under stress and how this may protect neural cell function. We also highlight the role (and potential contribution) of neuroglial LDs in aging and in neurologic disorders.

Keywords: astrocytes; lipid droplets; metabolic and oxidative stress; neuroglia; neurologic disorders; pathophysiology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Astrocyte–neuron coupling of lipid metabolism. During enhanced neuronal activity, L-lactate (lactate), produced in astrocytes from glucose in the process of aerobic glycolysis, is transported to neurons via monocarboxylate transporters (MCTs). In neurons, lactate is used in oxidative metabolism for ATP production and/or for de novo fatty acid (FA) synthesis. To avoid the toxicity of free FAs (FFAs), neurons release FFAs in apolipoprotein A/D (ApoE/D) particles, which can enter astrocytes via endocytosis. Once in astrocytes, FFAs are released from ApoE/D particles and are incorporated into lipid droplets (LDs). FAs released from LDs can be further used in astrocytes as a fuel in mitochondrial β-oxidation. Furthermore, in times of starvation, fasting, or intense exercise, astrocytes metabolize FFAs in the process of β-oxidation to produce ketone bodies (KBs) and shuttle them via MCTs to neuronal mitochondria for ATP synthesis, supporting neuronal energy metabolism. Astrocytes also synthesize lipids (FFAs and cholesterol (Chol)) de novo and/or release membrane-bound FAs and transfer them to neurons via Apo particles or FA transporters to be used as membrane components, supporting synaptic membranes and signaling.
Figure 2
Figure 2
Astrocytes under stress accumulate lipid droplets. Most lipid droplets in astrocytes are in contact with or in close proximity to mitochondria and the endoplasmic reticulum (ER). Metabolic stress (nutrient deprivation, excess free fatty acids [FFAs] or L-lactate), hypoxic stress, and noradrenaline, which activates the CNS stress response via activation of α2- and β-adrenergic receptors (ARs), increase the accumulation of lipid droplets in astrocytes. Accumulation of lipids in LDs in stressed cells promotes astrocyte energy production via mitochondrial β-oxidation and prevents FFA-induced lipotoxicity and ROS-mediated membrane lipid peroxidation, which increases the viability of cells under stress (adapted from Smolič et al. [37]).
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