{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:13:28Z","timestamp":1791281608686,"version":"4.1.0"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,2,1]]},"abstract":"<jats:p>Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids) exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The plasma cholesterol-lowering properties of PUFA are due partly to a diminution of cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the mechanisms involved, we examined how tuna fish oil and individual n\u22123 and n\u22126 PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that is subject to negative-feedback regulation by sterols, in co-ordination with HMG-CoA reductase. Feeding mice on a tuna fish oil diet for 2\u00a0weeks decreased serum cholesterol and triacylglycerol levels, by 50% and 60% respectively. Hepatic levels of FPP synthase and HMG-CoA reductase mRNAs were also decreased, by 70% and 40% respectively. Individual n\u22123 and n\u22126 PUFA lowered FPP synthase and HMG-CoA reductase mRNA levels in H4IIEC3 rat hepatoma cells to a greater extent than did stearate and oleate, with the largest inhibitory effects occurring with arachidonate, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). We observed a similar inhibitory effect on protein levels of FPP synthase. The suppressive effect of PUFA on the FPP synthase mRNA level was not due to a decrease in mRNA stability, but to transcription inhibition. Moreover, a lower nuclear availability of both SREBP-1 and SREBP-2 mature forms was observed in HepG2 human hepatoblastoma cells treated with arachidonate, EPA or DHA. Taken together, these data suggest that PUFA can down-regulate hepatic cholesterol synthesis through inhibition of HMG-CoA reductase and FPP synthase, at least in part through impairment of the SREBP pathway.<\/jats:p>","DOI":"10.1042\/bj20040933","type":"journal-article","created":{"date-parts":[[2005,1,24]],"date-time":"2005-01-24T10:04:26Z","timestamp":1106561066000},"page":"787-794","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids"],"prefix":"10.1042","volume":"385","author":[{"given":"Catherine","family":"LE\u00a0JOSSIC-CORCOS","sequence":"first","affiliation":[{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire (GDR CNRS no. 2583), Universit\u00e9 de Bourgogne, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"GONTHIER","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire (GDR CNRS no. 2583), Universit\u00e9 de Bourgogne, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"ZAGHINI","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire (GDR CNRS no. 2583), Universit\u00e9 de Bourgogne, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"LOGETTE","sequence":"additional","affiliation":[{"name":"Inserm U517, Facult\u00e9 de M\u00e9decine, 7 Bd Jeanne d'Arc, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishaiahu","family":"SHECHTER","sequence":"additional","affiliation":[{"name":"Department of Surgery, F. 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