Tags

Type your tag names separated by a space and hit enter

Peroxisome proliferator-activated receptor alpha is not rate-limiting for the lipoprotein-lowering action of fish oil.
J Biol Chem. 2001 Feb 16; 276(7):4634-9.JB

Abstract

Similar to fibrate hypolipidemic drugs, long chain polyunsaturated fatty acids contained in fish oil are activators of peroxisome proliferator-activated receptor alpha (PPARalpha). The goal of this study was to assess the contribution of PPARalpha in mediating the effect of fish oil on plasma lipid, lipoprotein, and apolipoprotein levels. To this end, PPARalpha-deficient mice and wild-type littermates were fed isocaloric fish oil or coconut oil diets, the content of which varied reciprocally between 0, 3, 7, and 10% for 1 week. In both wild-type and PPARalpha-deficient mice, fish oil feeding was associated with a dose-dependent decrease in triglycerides, cholesterol, and phospholipids associated with lower levels of very low density lipoprotein (VLDL) triglycerides and high density lipoprotein (HDL) cholesterol. The lowering of triglycerides and VLDL triglycerides was associated with a significant decrease of plasma apoC-III in both genotypes. Fish oil treatment did not influence hepatic apoC-III mRNA levels in either genotype indicating that apoC-III is not under transcriptional control by fish oil. The lowering of HDL cholesterol observed in both genotypes was associated with reduced plasma apoA-II without changes in liver apoA-II mRNA levels. In contrast, plasma apoA-I and liver apoA-I mRNA levels were decreased in wild-type but not in PPARalpha-deficient mice after fish oil feeding indicating that PPARalpha contributes to the effect of fish oil on apoA-I gene expression. In conclusion, PPARalpha is not rate-limiting for fish oil to exert its triglyceride- and HDL-lowering action. Furthermore, PPARalpha mediates, at least partly, the decrease of apoA-I after fish oil treatment, whereas apoC-III and apoA-II levels are affected in a PPARalpha-independent manner. Altogether, these results show major molecular differences in action between fibrates and fish oil providing a molecular rationale for combination treatment with these compounds.

Authors+Show Affiliations

Département d'Athérosclérose, INSERM U-508, and INSERM U-325, Institut Pasteur de Lille, 59019 Lille, France. jean.dallongeville@pasteur-lille.frNo affiliation info availableNo 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

11050100

Citation

Dallongeville, J, et al. "Peroxisome Proliferator-activated Receptor Alpha Is Not Rate-limiting for the Lipoprotein-lowering Action of Fish Oil." The Journal of Biological Chemistry, vol. 276, no. 7, 2001, pp. 4634-9.
Dallongeville J, Baugé E, Tailleux A, et al. Peroxisome proliferator-activated receptor alpha is not rate-limiting for the lipoprotein-lowering action of fish oil. J Biol Chem. 2001;276(7):4634-9.
Dallongeville, J., Baugé, E., Tailleux, A., Peters, J. M., Gonzalez, F. J., Fruchart, J. C., & Staels, B. (2001). Peroxisome proliferator-activated receptor alpha is not rate-limiting for the lipoprotein-lowering action of fish oil. The Journal of Biological Chemistry, 276(7), 4634-9.
Dallongeville J, et al. Peroxisome Proliferator-activated Receptor Alpha Is Not Rate-limiting for the Lipoprotein-lowering Action of Fish Oil. J Biol Chem. 2001 Feb 16;276(7):4634-9. PubMed PMID: 11050100.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferator-activated receptor alpha is not rate-limiting for the lipoprotein-lowering action of fish oil. AU - Dallongeville,J, AU - Baugé,E, AU - Tailleux,A, AU - Peters,J M, AU - Gonzalez,F J, AU - Fruchart,J C, AU - Staels,B, Y1 - 2000/10/24/ PY - 2000/10/26/pubmed PY - 2001/6/29/medline PY - 2000/10/26/entrez SP - 4634 EP - 9 JF - The Journal of biological chemistry JO - J Biol Chem VL - 276 IS - 7 N2 - Similar to fibrate hypolipidemic drugs, long chain polyunsaturated fatty acids contained in fish oil are activators of peroxisome proliferator-activated receptor alpha (PPARalpha). The goal of this study was to assess the contribution of PPARalpha in mediating the effect of fish oil on plasma lipid, lipoprotein, and apolipoprotein levels. To this end, PPARalpha-deficient mice and wild-type littermates were fed isocaloric fish oil or coconut oil diets, the content of which varied reciprocally between 0, 3, 7, and 10% for 1 week. In both wild-type and PPARalpha-deficient mice, fish oil feeding was associated with a dose-dependent decrease in triglycerides, cholesterol, and phospholipids associated with lower levels of very low density lipoprotein (VLDL) triglycerides and high density lipoprotein (HDL) cholesterol. The lowering of triglycerides and VLDL triglycerides was associated with a significant decrease of plasma apoC-III in both genotypes. Fish oil treatment did not influence hepatic apoC-III mRNA levels in either genotype indicating that apoC-III is not under transcriptional control by fish oil. The lowering of HDL cholesterol observed in both genotypes was associated with reduced plasma apoA-II without changes in liver apoA-II mRNA levels. In contrast, plasma apoA-I and liver apoA-I mRNA levels were decreased in wild-type but not in PPARalpha-deficient mice after fish oil feeding indicating that PPARalpha contributes to the effect of fish oil on apoA-I gene expression. In conclusion, PPARalpha is not rate-limiting for fish oil to exert its triglyceride- and HDL-lowering action. Furthermore, PPARalpha mediates, at least partly, the decrease of apoA-I after fish oil treatment, whereas apoC-III and apoA-II levels are affected in a PPARalpha-independent manner. Altogether, these results show major molecular differences in action between fibrates and fish oil providing a molecular rationale for combination treatment with these compounds. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11050100/Peroxisome_proliferator_activated_receptor_alpha_is_not_rate_limiting_for_the_lipoprotein_lowering_action_of_fish_oil_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11050100 DB - PRIME DP - Unbound Medicine ER -