{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:21:30Z","timestamp":1767612090476,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ultragenyx Pharmaceutical Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neutral lipid storage disease type M (NLSD-M) is an ultra-rare, autosomal recessive disorder that causes severe skeletal and cardiac muscle damage and lipid accumulation in all body tissues. In this hereditary pathology, the defective action of the adipose triglyceride lipase (ATGL) enzyme induces the enlargement of cytoplasmic lipid droplets and reduction in the detachment of mono- (MG) and diglycerides (DG). Although the pathogenesis of muscle fiber necrosis is unknown, some studies have shown alterations in cellular energy production, probably because MG and DG, the substrates of Krebs cycle, are less available. No tests have been tried with medium-chain fatty acid molecules to evaluate the anaplerotic effect in NLSD cells. In this study, we evaluated the in vitro effect of triheptanoin (Dojolvi\u00ae), a highly purified chemical triglyceride with seven carbon atoms, in fibroblasts obtained from five NLSD-M patients. Glycolytic and mitochondrial functions were determined by Seahorse XF Agylent Technology, and cellular viability and triglyceride content were measured through colorimetric assays. After the addition of triheptanoin, we observed an increase in glycolysis and mitochondrial respiration in all patients compared with healthy controls. These preliminary results show that triheptanoin is able to induce an anaplerotic effect in NLSD-M fibroblasts, paving the way towards new therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom13030452","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T02:28:17Z","timestamp":1677637697000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of Triheptanoin on Mitochondrial Respiration and Glycolysis in Cultured Fibroblasts from Neutral Lipid Storage Disease Type M (NLSD-M) Patients"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7682-862X","authenticated-orcid":false,"given":"Nelida In\u00e9s","family":"Noguera","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, TorVergata University of Rome, 00133 Rome, Italy"},{"name":"Unit of Neuro-Oncoematologia, Santa Lucia Foundation, IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-0068","authenticated-orcid":false,"given":"Daniela","family":"Tavian","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry and Molecular Biology, CRIBENS, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9554-8794","authenticated-orcid":false,"given":"Corrado","family":"Angelini","sequence":"additional","affiliation":[{"name":"Neuromuscular Lab, Department of Neurosciences, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Cortese","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Neurological Disease Center, Neurology Unit, San Filippo Neri Hospital, ASL Roma 1, 00135 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-7512","authenticated-orcid":false,"given":"Massimiliano","family":"Filosto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, 25121 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1830-2886","authenticated-orcid":false,"given":"Matteo","family":"Garibaldi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Neurological Disease Centre, Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), SAPIENZA University of Rome, Sant\u2019Andrea Hospital, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-6698","authenticated-orcid":false,"given":"Sara","family":"Missaglia","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry and Molecular Biology, CRIBENS, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariela","family":"Smigliani","sequence":"additional","affiliation":[{"name":"Unit of Neuro-Oncoematologia, Santa Lucia Foundation, IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Zaza","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, TorVergata University of Rome, 00133 Rome, Italy"},{"name":"Unit of Neuro-Oncoematologia, Santa Lucia Foundation, IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-6855","authenticated-orcid":false,"given":"Elena Maria","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Neurological Disease Center, Neurology Unit, San Filippo Neri Hospital, ASL Roma 1, 00135 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.nmd.2010.04.004","article-title":"Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene","volume":"20","author":"Akman","year":"2010","journal-title":"Neuromuscul. 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