Tags

Type your tag names separated by a space and hit enter

Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids.
Biochem J. 2005 Feb 01; 385(Pt 3):787-94.BJ

Abstract

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-3 and n-6 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 weeks 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-3 and n-6 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.

Authors+Show Affiliations

Laboratoire de Biologie Moléculaire et Cellulaire (GDR CNRS no. 2583), Université de Bourgogne, 21000 Dijon, France. catherine.corcos@univ-brest.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15473864

Citation

Le Jossic-Corcos, Catherine, et al. "Hepatic Farnesyl Diphosphate Synthase Expression Is Suppressed By Polyunsaturated Fatty Acids." The Biochemical Journal, vol. 385, no. Pt 3, 2005, pp. 787-94.
Le Jossic-Corcos C, Gonthier C, Zaghini I, et al. Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids. Biochem J. 2005;385(Pt 3):787-94.
Le Jossic-Corcos, C., Gonthier, C., Zaghini, I., Logette, E., Shechter, I., & Bournot, P. (2005). Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids. The Biochemical Journal, 385(Pt 3), 787-94.
Le Jossic-Corcos C, et al. Hepatic Farnesyl Diphosphate Synthase Expression Is Suppressed By Polyunsaturated Fatty Acids. Biochem J. 2005 Feb 1;385(Pt 3):787-94. PubMed PMID: 15473864.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids. AU - Le Jossic-Corcos,Catherine, AU - Gonthier,Céline, AU - Zaghini,Isabelle, AU - Logette,Emmanuelle, AU - Shechter,Ishaiahu, AU - Bournot,Paulette, PY - 2004/10/12/pubmed PY - 2005/7/30/medline PY - 2004/10/12/entrez SP - 787 EP - 94 JF - The Biochemical journal JO - Biochem J VL - 385 IS - Pt 3 N2 - 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-3 and n-6 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 weeks 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-3 and n-6 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. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/15473864/Hepatic_farnesyl_diphosphate_synthase_expression_is_suppressed_by_polyunsaturated_fatty_acids_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20040933 DB - PRIME DP - Unbound Medicine ER -