Elsevier

Clinical Nutrition

Volume 27, Issue 3, June 2008, Pages 424-430
Clinical Nutrition

Original article
Omega-3 fatty acid containing diets decrease plasma triglyceride concentrations in mice by reducing endogenous triglyceride synthesis and enhancing the blood clearance of triglyceride-rich particles

https://doi.org/10.1016/j.clnu.2008.02.001Get rights and content

Summary

Background & aims

Intake of n-3 fatty acids can reduce both fasting and postprandial triglyceride (TG) concentrations in humans as well as in experimental animals, but the mechanisms by which this occurs are not completely known. We investigated in mice the effects of dietary fish oil (a source of n-3 fatty acids) on endogenous TG synthesis and exogenous TG-rich particle removal.

Methods

C57 BL/6J mice were fed for 4 months with three types of high-fat diets (18% fat wt/wt) – soy oil, fish oil and a mixture of soy oil and fish oil (soy/fish) (5:1 wt/wt), and a chow diet with 6% fat from soy oil (wt/wt) served as a control. Plasma TG and apolipoprotein B (apoB) concentrations and lipoprotein lipase (LPL) activity were measured. Triton WR 1339 was used to assess hepatic synthesis of very low density lipoprotein, and intravenous injection of chylomicron-like lipid emulsions was conducted to determine the effects of dietary fish oil n-3 fatty acids on exogenous TG clearance.

Results

Both fish and soy/fish oil diets reduced plasma TG levels in fed and fasted states compared to soy oil alone. Plasma pre- and post-heparin LPL activities were significantly higher with fish and soy/fish oil diets than soy oil diet in fed mice. No differences in plasma TG levels and LPL activity were shown among groups of fish oil, soy/fish oil and normal chow diets. Levels of hepatic TG and apoB synthesis were 30–50% and 42% lower in mice fed with the fish oil diet compared to the other three diets. In addition, compared to soy oil diet, fish oil feeding significantly increased blood clearance of chylomicron-like lipid emulsions by 21–26%.

Conclusions

Our data suggest that reduced endogenous TG synthesis, increased LPL activities and more rapid blood clearance of TG-rich particles all distinctly contribute to the TG-lowering effects of fish oil n-3 fatty acids.

Introduction

Hypertriglyceridemia, the most common type of dyslipidemia, is a risk factor for progression of atherosclerosis and a strong independent predictor of future myocardial infarction.1, 2 Consumption of n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present in high amounts in some fish oil, reduce both fasting and postprandial triglyceride (TG) concentrations in humans as well as in experimental animals.2 n-3 fatty acids are used for treatment of patients with dyslipidemia. Recommendations from the American Heart Association include ingesting more fish oil n-3 fatty acids for patients with coronary heart diseases and hypertriglyceridemia.3, 4 However, the mechanisms of TG-reducing effects of n-3 fatty acids have not been fully determined and conflicting observations exist on some of these pathways.

There is a large body of evidence which shows that n-3 fatty acids reduce plasma TG concentrations through reduced endogenous very low density lipoprotein production.2, 5, 6, 7, 8 This does not preclude a contribution of enhanced TG-rich lipoprotein clearance, which may be mediated through altered particle size, structure or chemical composition9, 10 or altered lipoprotein lipase (LPL) activity and mass.2, 8 It has been suggested that n-3 fatty acids increase LPL or hepatic lipase (HL) activity,11, 12 but several investigators demonstrated that n-3 fatty acids do not affect or even decrease the enzymes' activity.13, 14, 15 Regarding the effects of n-3 fatty acids on TG-rich lipoprotein clearance, some researchers reported accelerated chylomicron TG clearance16, 17, 18 but no changes were found by others.5, 19, 20 In mouse models, we have reported faster clearance of n-3 TG enriched lipid emulsions as compared to n-6 rich emulsions.9, 10 The controversy in the mechanisms of TG-reducing effects of n-3 fatty acids may possibly be ascribed to differences in subjects (human vs. animals), content of n-3 fatty acids, TG composition in diets, duration of experiments, or other factors.

Human diets have changed greatly in the past 50–100 years, especially in the types of fat and fatty acids ingested.21 In modern society more saturated fat, n-6 fatty acids and trans fatty acids are being consumed with decreases in n-3 fatty acid intake: changes which may have contributed to increases in nutrition-related chronic diseases, including cardiovascular diseases, diabetes, obesity, cancer, immune-related diseases, and others. An appropriate ratio of n-3 to other fatty acids in diet is an important determinant of human health.21 To date, in most studies, the quantity of fish oil accounts for less than 10% of total fat intake; also only some of the potential metabolic effects of dietary n-3 fatty acids have been examined. In the present study, we utilized high-fat diets containing 15% of fat as fish oil and also pure fish oil to delineate their effects on TG metabolism, including LPL activities, hepatic TG synthesis and removal of exogenous chylomicron-like lipid emulsions using a mouse model.

Section snippets

Diets

Three dietary regimes with high-fat (18% fat wt/wt) – soy oil, fish oil and mixture of soy oil and fish oil (soy/fish) (5:1 wt/wt) and a control chow diet (6% fat from soy oil, wt/wt) were used. Each of the three high-fat diets was designed with the same baseline containing 230 g of casein, 180 g of corn starch, 150 g of maltodextrin, 150 g of sucrose, 40 g of mineral mix (AIN-93G-MX), 11 g of vitamin mix (AIN-93-VX), 47 g of cellulose, 4.6 g of calcium phosphate and 5.2 g of choline per kilogram. In

Effects of dietary fish oil on plasma TG levels

In both fed and fasted states, plasma TG levels in fish oil group (0.33 ± 0.06 and 0.23 ± 0.06 mmol/L) and soy/fish oil group (0.39 ± 0.05 and 0.19 ± 0.06 mmol/L) were both substantially lower than in soy oil group (0.68 ± 0.18 and 0.59 ± 0.17 mmol/L) (P < 0.001), and were very similar to the control group on a normal chow diet (0.40 ± 0.05 mmol/L and 0.20 ± 0.05 mmol/L) (P > 0.05) (Fig. 1).

Effects of dietary fish oil on activities of LPL in plasma

LPL, the key enzyme in TG lipolysis, plays an important role in maintaining blood TG concentration. Thus, we analyzed the LPL

Discussion

Fish oil enriched with n-3 fatty acids exerts beneficial effects on human health, including plasma TG-lowering.2, 3, 4, 24 In this study, using mouse models fed high-fat diets with different fatty acid compositions, we found that diets containing pure fish oil or 15% of fish oil in terms of total fat significantly reduced plasma TG concentrations by 40–60% both in fasting and postprandial states.

The hypotriglyceridemic action of n-3 fatty acids has been attributed to their inhibition on

Conflict of interest statement

There are no financial conflicts of interest for all authors.

Acknowledgements

This work was supported by National Natural Science Foundation of China (NSFC) (30200303) (K.Q.) and the Scientific Research Foundation for the Returned Oversees Chinese Scholars, State Education Ministry (2002) (K.Q.), and by NIH grant HL40404 (R.J.D.).

References (34)

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