{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:25:17Z","timestamp":1792182317691,"version":"4.4.0"},"reference-count":54,"publisher":"The Company of Biologists","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>Lipid droplet formation and subsequent steatosis (the abnormal retention of lipids within a cell) has been reported to contribute to hepatotoxicity and is an adverse effect of many pharmacological agents including the antiepileptic drug valproic acid (VPA). In this study, we have developed a simple model system (Dictyostelium discoideum) to investigate the effects of VPA and related compounds in lipid droplet formation. In mammalian hepatocytes, VPA increases lipid droplet accumulation over a 24-hour period, giving rise to liver cell damage, and we show a similar effect in Dictyostelium following 30 minutes of VPA treatment. Using 3H-labelled polyunsaturated (arachidonic) or saturated (palmitic) fatty acids, we shown that VPA treatment of Dictyostelium gives rise to an increased accumulation of both types of fatty acids in phosphatidylcholine, phosphatidylethanolamine and non-polar lipids in this time period, with a similar trend observed in human hepatocytes (Huh7 cells) labelled with [3H]arachidonic acid. In addition, pharmacological inhibition of \u03b2-oxidation in Dictyostelium phenocopies fatty acid accumulation, in agreement with data reported in mammalian systems. Using Dictyostelium, we then screened a range of VPA-related compounds to identify those with high and low lipid-accumulation potential, and validated these activities for effects on lipid droplet formation by using human hepatocytes. Structure-activity relationships for these VPA-related compounds suggest that lipid accumulation is independent of VPA-catalysed teratogenicity and inositol depletion. These results suggest that Dictyostelium could provide both a novel model system for the analysis of lipid droplet formation in human hepatocytes and a rapid method for identifying VPA-related compounds that show liver toxicology.<\/jats:p>","DOI":"10.1242\/dmm.008391","type":"journal-article","created":{"date-parts":[[2011,10,15]],"date-time":"2011-10-15T04:01:52Z","timestamp":1318651312000},"page":"231-240","source":"Crossref","is-referenced-by-count":19,"title":["Conserved valproic-acid-induced lipid droplet formation in <i>Dictyostelium<\/i> and human hepatocytes identifies structurally active compounds"],"prefix":"10.1242","volume":"5","author":[{"given":"Lucy M.","family":"Elphick","sequence":"first","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Science, Royal Holloway University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Pawolleck","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Science, Royal Holloway University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Guschina","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Chaieb","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Science, Royal Holloway University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eikel","sequence":"additional","affiliation":[{"name":"Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Nau","sequence":"additional","affiliation":[{"name":"Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Harwood","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick J.","family":"Plant","sequence":"additional","affiliation":[{"name":"Centre for Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin S. 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