{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:07:22Z","timestamp":1791526042956,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG081421"],"award-info":[{"award-number":["R01AG081421"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG080589"],"award-info":[{"award-number":["R01AG080589"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM148326"],"award-info":[{"award-number":["P20 GM148326"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lipid droplets (LDs) are emerging as key regulators of metabolism and inflammation, with their buildup in microglia linked to aging and neurodegeneration. Perilipin-2 (Plin2) is a ubiquitously expressed LD-associated protein that stabilizes lipid stores; in peripheral tissues, its upregulation promotes lipid retention, inflammation, and metabolic dysfunction. Yet, its role in microglia remains unclear. Using CRISPR-engineered Plin2 knockout (KO) BV2 microglia, we examined how Plin2 contributes to lipid accumulation, bioenergetics, and immune function. Compared to wild-type (WT) cells, Plin2 KO microglia showed markedly reduced LD burden under basal and oleic acid-loaded conditions. Functionally, this was linked to enhanced phagocytosis of zymosan particles, even after lipid loading, indicating improved clearance capacity. Transcriptomics revealed genotype-specific responses to amyloid-\u03b2 (A\u03b2), especially in mitochondrial metabolism pathways. Seahorse assays confirmed a distinct bioenergetic profile in KO cells, with reduced basal respiration and glycolysis but preserved mitochondrial capacity, increased spare reserve, and a blunted glycolytic response to A\u03b2. Together, these findings establish Plin2 as a regulator of microglial lipid storage and metabolic state, with its loss reducing lipid buildup, enhancing phagocytosis, and altering A\u03b2-induced metabolic reprogramming. Targeting Plin2 may represent a strategy to reprogram microglial metabolism and function in aging and neurodegeneration.<\/jats:p>","DOI":"10.3390\/cells14221783","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:57:13Z","timestamp":1763038633000},"page":"1783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Knockout of Perilipin-2 in Microglia Alters Lipid Droplet Accumulation and Response to Alzheimer\u2019s Disease Stimuli"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7070-1805","authenticated-orcid":false,"given":"Isaiah O.","family":"Stephens","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0134-7586","authenticated-orcid":false,"given":"Lance A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington, KY 40508, USA"},{"name":"Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat. 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