Pharmacological Upregulation of Microglial Lipid Droplet Alleviates Neuroinflammation and Acute Ischemic Brain Injury
Open accessAbstract
Lipid droplets (LDs) were reported to play an important role in the modulation of inflammation and various cellular processes among multiple cell types. However, LDs accumulation, its function and mechanisms of its formation during ischemic stroke remained poorly-identified. In this study, we observed increased LDs accumulation in microglia at the acute stage of ischemic stroke by immunofluorescence and flow cytometry. Transcriptomic analysis indicated that microglia accumulated with LDs were associated with inflammation and phagocytosis. Both inflammatory activation and phagocytosis of tissue debris in microglia could contribute to LDs formation. Moreover, through specific LDs depletion and overload experiments by pharmacological approaches, we proposed that LDs was critical for the maintenance of anti-inflammatory properties of microglia. Furthermore, Atglistatin, a specific adipose triglyceride lipase (ATGL) inhibitor, was shown to prevent proinflammatory cytokines production in primary microglia through decreased LDs lipolysis. After Atglistatin treatment, middle cerebral artery occlusion (MCAO) mice showed decreased infarct volume and improved neurobehavioral performance at the acute stage of stroke. Our findings provided a biological basis for microglial LDs regulation as a potential therapeutic strategy for acute ischemic stroke and uncovered the neuroprotective role of Atglistatin in the treatment of MCAO mice.
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In ischemic brain injury, lipid droplets mitigate the microglial pro-inflammatory response, decrease infarct volume, and improve neurobehavioral performance.
“In ischemic brain injury, for instance, LDs mitigate the microglial pro-inflammatory response, decrease infarct volume, and improve their neurobehavioral performance (63, 64).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [64]
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Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model
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“In ischemic brain injury, for instance, LDs mitigate the microglial pro-inflammatory response, decrease infarct volume, and improve their neurobehavioral performance ( 63 , 64 ).”
- Authors
- Li, H., Liu, P., Deng, S., Zhu, L., Cao, X., Bao, X., Xia, S., Xu, Y., & Zhang, B.
- Affiliations
- Nanjing Drum Tower Hospital (CN)
- Corresponding author
- Zhang, Bing
- Venue
- Inflammation
- Published
- 2023-07-14
- Volume
- 46
- Issue
- 5
- Pages
- 1832-1848
- ISSN
- 0360-3997 (ISSN-L)
- 1573-2576
- PMC
- PMC10567859
- OpenAlex
- W4384339295
- Cited by
- 43
- References
- 52
- Citations by year
- 2026: 12 · 2025: 25 · 2024: 6
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Inflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Jiangsu Province (BK20220180)
- National Science and Technology Innovation 2030--Major program of "Brain Science and Brain-Like Research" (2022ZD0211800)
- National Natural Science Foundation of China (81720108022)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- acute ischemic stroke, neuroinflammation, microglial phagocytosis, inflammatory cytokines, middle cerebral artery occlusion, neuroprotection, infarct size
- MeSH terms
- Ischemic Stroke, Neuroinflammatory Diseases, Animals, Brain Injuries, Brain Ischemia, Inflammation, Phenylurea Compounds, Up-Regulation, Microglia, Infarction, Middle Cerebral Artery, Mice, Lipid Droplets
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