{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:11Z","timestamp":1792789091225,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["NS37355"],"award-info":[{"award-number":["NS37355"]}]},{"name":"NIH","award":["HD10981"],"award-info":[{"award-number":["HD10981"]}]},{"name":"NIH","award":["HD24061"],"award-info":[{"award-number":["HD24061"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>\u201cBubblegum\u201d acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during mouse brain development, facilitating the activation of long-chain fatty acids (LCFA) and their incorporation into lipid species that are crucial for brain function. ACSBG1 converts LCFA into acyl-CoA derivatives, supporting vital metabolic processes. Fruit fly mutants lacking ACSBG1 exhibited neurodegeneration and had elevated levels of very long-chain fatty acids (VLCFA), characteristics of human X-linked adrenoleukodystrophy (XALD). To explore ACSBG1\u2019s function and potential as a therapeutic target in XALD, we created an ACSBG1 knockout (Acsbg1\u2212\/\u2212) mouse and examined the effects on brain FA metabolism during development. Phenotypically, Acsbg1\u2212\/\u2212 mice resembled wild type (w.t.) mice. ACSBG1 expression was found mainly in tissue affected pathologically in XALD, namely the brain, adrenal gland and testis. ACSBG1 depletion did not significantly reduce the total ACS enzyme activity in these tissue types. In adult mouse brain, ACSBG1 expression was highest in the cerebellum; the low levels detected during the first week of life dramatically increased thereafter. Unexpectedly, lower, rather than higher, saturated VLCFA levels were found in cerebella from Acsbg1\u2212\/\u2212 vs. w.t. mice, especially after one week of age. Developmental changes in monounsaturated \u03c99 FA and polyunsaturated \u03c93 FA levels also differed between w.t. and Acsbg1\u2212\/\u2212 mice. ACSBG1 deficiency impacted the developmental expression of several cerebellar FA metabolism enzymes, including those required for the synthesis of \u03c93 polyunsaturated FA, precursors of bioactive signaling molecules like eicosanoids and docosanoids. These changes in membrane lipid FA composition likely affect membrane fluidity and may thus influence the body\u2019s response to inflammation. We conclude that, despite compelling circumstantial evidence, it is unlikely that ACSBG1 directly contributes to the pathology of XALD, decreasing its potential as a therapeutic target. Instead, the effects of ACSBG1 knockout on processes regulated by eicosanoids and\/or docosanoids should be further investigated.<\/jats:p>","DOI":"10.3390\/cells13201687","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T05:47:58Z","timestamp":1728884878000},"page":"1687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of ACSBG1 in Brain Lipid Metabolism and X-Linked Adrenoleukodystrophy Pathogenesis: Insights from a Knockout Mouse Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiaoli","family":"Ye","sequence":"first","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Genetic Medicine and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-241X","authenticated-orcid":false,"given":"Domingo","family":"Gonz\u00e1lez-Lamu\u00f1o","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengtong","family":"Pei","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9147-1902","authenticated-orcid":false,"given":"Ann B.","family":"Moser","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirby D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Genetic Medicine and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0163-7827(97)00004-0","article-title":"Fatty acid activation","volume":"36","author":"Watkins","year":"1997","journal-title":"Prog. Lipid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1194\/jlr.M700378-JLR200","article-title":"Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome","volume":"48","author":"Watkins","year":"2007","journal-title":"J. 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