{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:57:06Z","timestamp":1790632626027,"version":"4.1.0"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Nutr"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoketotic hypoglycaemia is a biochemical hallmark of glycogen storage disease type 1 (GSD1). This is due to inhibition of carnitine-palmitoyl transferase 1 by malonyl-CoA. This inhibits the influx of long-chain fatty acids into the mitochondrial matrix for fatty acid oxidation. This leads to reduced hepatic ketogenesis and impaired energy production in the liver and kidney. Hypoketotic hypoglycaemia may result in CNS symptoms due to energy depletion.<\/jats:p><jats:p>Recently, it was reported that enzymes involved in mitochondrial long-chain fatty acid oxidation are upregulated in PBMC from patients suffering from GSD1.<\/jats:p><jats:p>I suggest that administration of the prodrug bempedoic acid results in reduced production of malonyl-CoA by inhibiting the ATP-citrate lyase, thus releasing the block of mitochondrial long-chain fatty acid influx. These fatty acids could make use of the increased capacity of fatty acid oxidation as observed in PBMC recently. In the liver, ketogenesis is activated, and energy production is increased in both the liver and kidney. This could result in improved metabolic control and avoidance of cerebral energy depletion.<\/jats:p><jats:p>Bempedoic acid is approved as medication in adult patients with hypercholesterolaemia and mixed dyslipidaemia. Repurposing bempedoic acid for the use in GSD1 may improve metabolic control in GSD1.<\/jats:p>","DOI":"10.1186\/s12263-023-00733-2","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T13:02:48Z","timestamp":1695042168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From common to rare: repurposing of bempedoic acid for the treatment of glycogen storage disease type 1"],"prefix":"10.1186","volume":"18","author":[{"given":"Anibh M.","family":"Das","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"issue":"1","key":"733_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12263-023-00729-y.PMID:37280548;PMCID:PMC10245432","volume":"18","author":"A Rossi","year":"2023","unstructured":"Rossi A, Assunto A, Rosano C, Tucci S, Ruoppolo M, Caterino M, Pirozzi F, Strisciuglio P, Parenti G, Melis D. Mitochondrial reprogramming in peripheral blood mononuclear cells of patients with glycogen storage disease type Ia. Genes Nutr. 2023;18(1):10. https:\/\/doi.org\/10.1186\/s12263-023-00729-y.PMID:37280548;PMCID:PMC10245432.","journal-title":"Genes Nutr"},{"key":"733_CR2","doi-asserted-by":"publisher","unstructured":"Kishnani PS, Austin SL, Abdenur JE et al. American College of Medical Genetics and Genomics. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med 2014;16(11):e1. https:\/\/doi.org\/10.1038\/gim.2014.128. PMID: 25356975.","DOI":"10.1038\/gim.2014.128"},{"key":"733_CR3","doi-asserted-by":"publisher","first-page":"3828","DOI":"10.3390\/nu13113828.PMID:34836082;PMCID:PMC8621617","volume":"13","author":"TGJ Derks","year":"2021","unstructured":"Derks TGJ, Rodriguez-Buritica DF, Ahmad A, et al. Glycogen storage disease type Ia: current management options, burden and unmet needs. Nutrients. 2021;13:3828. https:\/\/doi.org\/10.3390\/nu13113828.PMID:34836082;PMCID:PMC8621617.","journal-title":"Nutrients"},{"key":"733_CR4","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1172\/jci63967.PMID:22833869;PMCID:PMC3366419","volume":"122","author":"DW Foster","year":"2012","unstructured":"Foster DW. Malonyl-CoA: the regulator of fatty acid synthesis and oxidation. J Clin Invest. 2012;122:1958\u20139. https:\/\/doi.org\/10.1172\/jci63967.PMID:22833869;PMCID:PMC3366419.","journal-title":"J Clin Invest"},{"key":"733_CR5","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1159\/000283242","volume":"56","author":"AM Das","year":"2010","unstructured":"Das AM, L\u00fccke T, Meyer U, Hartmann H, Illsinger S. Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth. Ann Nutr Metab. 2010;56:225\u201332. https:\/\/doi.org\/10.1159\/000283242. (Epub 2010 Mar 30 PMID: 20357432).","journal-title":"Ann Nutr Metab"},{"issue":"7","key":"733_CR6","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1002\/mnfr.201100685","volume":"56","author":"VD de Mello","year":"2012","unstructured":"de Mello VD, Kolehmanien M, Schwab U, Pulkkinen L, Uusitupa M. Gene expression of peripheral blood mononuclear cells as a tool in dietary intervention studies: what do we know so far? Mol Nutr Food Res. 2012;56(7):1160\u201372. https:\/\/doi.org\/10.1002\/mnfr.201100685. (Epub 2012 May 18 PMID: 22610960).","journal-title":"Mol Nutr Food Res"},{"key":"733_CR7","doi-asserted-by":"publisher","unstructured":"Ballantyne CM, Bays H, Catapano AL, Goldberg A, Ray KK, Saseen JJ. Role of bempedoic acid in clinical practice. Cardiovasc Drugs Ther 2021;35:853\u201364. https:\/\/doi.org\/10.1007\/s10557-021-07147-5. Epub 2021 Apr 5. Erratum in: Cardiovasc Drugs Ther. 2021 Apr 19;: PMID: 33818688; PMCID: PMC8266788.","DOI":"10.1007\/s10557-021-07147-5"},{"key":"733_CR8","doi-asserted-by":"publisher","first-page":"1028355","DOI":"10.3389\/fcvm.2022.1028355.PMID:36386319;PMCID:PMC9650075","volume":"9","author":"G Biolo","year":"2022","unstructured":"Biolo G, Vinci P, Mangogna A, et al. Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome. Front Cardiovasc Med. 2022;9:1028355. https:\/\/doi.org\/10.3389\/fcvm.2022.1028355.PMID:36386319;PMCID:PMC9650075.","journal-title":"Front Cardiovasc Med"},{"key":"733_CR9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/MOL.0000000000000390","volume":"28","author":"AC Burke","year":"2017","unstructured":"Burke AC, Huff MW. ATP-citrate lyase: genetics, molecular biology and therapeutic target for dyslipidemia. Curr Opin Lipidol. 2017;28:193\u2013200. https:\/\/doi.org\/10.1097\/MOL.0000000000000390. (PMID: 28059952).","journal-title":"Curr Opin Lipidol"}],"container-title":["Genes &amp; Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12263-023-00733-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12263-023-00733-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12263-023-00733-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:03:44Z","timestamp":1700265824000},"score":1,"resource":{"primary":{"URL":"https:\/\/genesandnutrition.biomedcentral.com\/articles\/10.1186\/s12263-023-00733-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,18]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["733"],"URL":"https:\/\/doi.org\/10.1186\/s12263-023-00733-2","relation":{},"ISSN":["1555-8932","1865-3499"],"issn-type":[{"value":"1555-8932","type":"print"},{"value":"1865-3499","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,18]]},"assertion":[{"value":"19 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15"}}