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.
Highlights
Similar to fibrate hypolipidemic drugs, long chain polyunsaturated fatty acids contained in fish oil are activators of peroxisome proliferator-activated receptor ␣ (PPAR␣)
Effect of Fenofibrate and Fish Oil on Liver Acyl-CoA Oxidase, ApoA-I, ApoA-II, and ApoC-III mRNA Levels in SV129 Mice Strain—To test whether mice of the SV129 strain respond to PPAR␣ activators by peroxisomal proliferation and apolipoprotein gene expression changes, the effect of fenofibrate (0.2% w/w) and fish oil (10% w/w) on liver acyl-CoA oxidase, apoC-III, apoA-I, and apoA-II mRNA levels were analyzed (Fig. 1)
Liver acyl-CoA oxidase mRNA levels were higher in SV129 mice treated with fenofibrate than in those supplemented with coconut oil
Summary
Similar to fibrate hypolipidemic drugs, long chain polyunsaturated fatty acids contained in fish oil are activators of peroxisome proliferator-activated receptor ␣ (PPAR␣). The goal of this study was to assess the contribution of PPAR␣ in mediating the effect of fish oil on plasma lipid, lipoprotein, and apolipoprotein levels To this end, PPAR␣-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. The goal of the present study was to assess the role of the PPAR␣ pathway in mediating the fish oil-dependent lipid, lipoprotein and apolipoprotein alterations To this end, the effects of increasing consumption of fish oil on lipid and apolipoprotein levels were assessed in wild-type and very low density lipoprotein; PPAR␣, peroxisome proliferator-activated receptor ␣; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; FPLC, fast protein liquid chromatography; PIPES, 1,4-piperazinediethanesulfonic acid. Fish oil acts differently than synthetic PPAR␣ activators such as fibrates
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
