Cited by 184Lipid metabolism and biosynthesisNeuroinflammation and Neurodegeneration MechanismsNeurological diseases and metabolism

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Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases

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Yang, Danying, Wang, Xifeng, Zhang, Lieliang, Fang, Yang, Zheng, Qingcui, Liu, Xing, Yu, Wen, Chen, Shoulin, Ying, Jun, Hua, Fuzhou·2022·Cell & Bioscience

DOI 10.1186/s13578-022-00828-0PMC PMC9277953

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Abstract

The importance of neuroglia in maintaining normal brain function under physiological and pathological conditions has been supported by growing evidence in recent years. The most important issues regarding glial metabolism and function include the cooperation between glial populations and neurons, morphological and functional changes in pathological states, and the role in the onset and progression of neurodegenerative diseases. Although lipid accumulation and further lipid droplet production in neurodegenerative disease brain models have been observed for a long time, the dynamic development of brain lipid droplet research in recent years suggests its role in the development and progression of neurodegenerative diseases was previously underestimated. First recognized as organelles of lipid storage, lipid droplets (LDs) have emerged as an important organelle in metabolic diseases, inflammation, and host defense. Dynamic changes in lipid metabolism within neurons and glial cells resulting in lipid accumulation and lipid droplet formation are present in brain models of various neurodegenerative diseases, yet their role in the brain remains largely unexplored. This paper first reviews the metabolism and accumulation of several major lipids in the brain and discusses the regulation of lipid accumulation in different types of brain cells. We explore the potential role of intracellular lipid accumulation in the pathogenesis of neurodegeneration, starting from lipid metabolism and LDs biogenesis in glial cells, and discuss several pathological factors that promote lipid droplet formation, mainly focusing on oxidative stress, energy metabolism and glial cell-neuron coupling, which are closely related to the etiology and progression of neurodegenerative diseases. Finally, the directions and challenges of intracellular lipid metabolism in glial cells in neurodegeneration are discussed.

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Fig. 1 Astrocyte-neuron coupling in lipid metabolism. A Exogenous lactate may enter astrocytes and neurons through lactate MCTs, moreover, the reduction of MCT levels delayed neurodegeneration. B Glia-derived lactate is decarboxylated in neuronal mitochondria and the resulting acetyl-CoA generates FAs that are shuttled back to the glial compartment, where they accumulate in LDs. C Due to the low capacity of neurons to utilize LDs, it translocates excess FAs into astrocytes via vesicles containing apolipoprotein E-like particles. D Neuron-derived FAs are delivered to astrocyte LDs that protect astrocytes from the lipotoxicity of FAs. E Astrocytes can use FFAs during β-oxidation and provide the energy generated during β-oxidation to mitochondriaCC BY · PubMed Central

Fig. 2 Two possible antagonistic effects of Mitochondria contact LDs. A DGAT2 was found to co-localize with the attachment of lipid droplet surface and mitochondria, and it may play a role in facilitating the binding of LDs to mitochondria. B Perilipins are LD-scaffolding proteins, PLIN-5 recruits mitochondria to the LD surface through a C-terminal region, while down-regulation of PLIN-5 expression reduces the contact of mitochondria with LDs. C MIGA2 is an outer mitochondrial membrane protein that can link mitochondria to LDs through a specific region of its C terminus. D Mitochondria anchored to LDs exhibit reduced motility and fission, the specific interaction between PLIN1 and MFN2 may promote mitochondria–LDs interaction by enhancing cellular responsiveness to lipolysis. In addition to that, the knockdown of MFN1 and OPA1 resulted in the separation of mitochondria with LDs. E Marf is required to be in contact with LDs to store cholesterol, neuronal cholesterol reduction induces p-Tau degradation by enhancing proteasome levels and increasing total cellular proteasome activity. F Underfed conditions, lipolysis is activated by LD-associated lipases, such as ATGL, HSL, and MGL, which promote the breakdown of TAG to FAs. Then, FAs are transported to mitochondria for β-oxidationCC BY · PubMed Central

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Authors: Yang, D., Wang, X., Zhang, L., Fang, Y., Zheng, Q., Liu, X., Yu, W., Chen, S., Ying, J., & Hua, F.
Affiliations: Second Affiliated Hospital of Nanchang University (CN)
First Affiliated Hospital of Nanchang University (CN)
Corresponding author: Ying, Jun
Hua, Fuzhou
ORCID: Wang, Xifeng
Zhang, Lieliang
Liu, Xing
Yu, Wen
Chen, Shoulin
Ying, Jun
Hua, Fuzhou
Venue: Cell & Bioscience
Publisher: Springer Science and Business Media LLC
Published: 2022-07-12
Volume: 12
Issue: 1
Pages: 106-106
ISSN: 2045-3701 (ISSN-L)
DOI: 10.1186/s13578-022-00828-0
PMC: PMC9277953
OpenAlex: W4285093609
Cited by: 179
References: 135
Citations by year: 2026: 46 · 2025: 64 · 2024: 40 · 2023: 28 · 2022: 1
FWCI: 3.60
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Cell & Bioscience (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (82060219, 81860259)
Natural Science Foundation of Jiangxi Province (20212ACB216009, 20202BAB206033, 20212BAB216048)
Nanchang University (20192BAB215042)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords: glial cells, lipid metabolism, lipid droplets, neurodegenerative diseases, brain development, lipid accumulation, oxidative stress, energy metabolism, lipid droplet formation, intracellular lipid metabolism

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Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases

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