Distinct regulation of plasma LDL cholesterol by eicosapentaenoic acid and docosahexaenoic acid in high fat diet-fed hamsters: Participation of cholesterol ester transfer protein and LDL receptor

Ishida, Takayuki; Ohta, Masahiko; Nakakuki, Masanori; Kami, Hideaki; Uchiyama, Ryota; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Shimano, Hitoshi

doi:10.1016/j.plefa.2013.01.001

Cited by 36 publications

(22 citation statements)

References 31 publications

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“…18 Icosapent ethyl is a high-concentration EPA prescription product and its biologic effects may differ from dietary supplements and other prescription omega-3 fatty acid products that contain variable amounts of EPA and the omega-3 fatty acid docosahexaenoic acid (DHA), which may increase LDL-C levels in some patients. 19e21 Potential mechanisms for the LDL-C increase observed with DHA, but not EPA, include differences in how EPA and DHA affect LDL clearance (DHA has been found to increase cholesteryl ester transfer protein activity and decrease LDL receptor expression in an animal model 22 and to downregulate the LDL receptor gene in humans 23 ), DHA-mediated increased conversion of VLDL to LDL, and DHA-mediated increased LDL particle size. 24 Omega-3 fatty acid dietary supplements have been documented to not only have variable/inconsistent amounts of omega 3 fatty acids but also high saturated fat content and oxidation products.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials)

Mosca

Ballantyne

Bays

et al. 2017

The American Journal of Cardiology

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There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200-2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (-22.7%; p = 0.0327) and ANCHOR (-21.5%; p <0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non-high-density lipoprotein cholesterol levels in MARINE (-15.7%; p = 0.0082) and ANCHOR (-14.2%; p <0.0001) and total cholesterol levels in MARINE (-14.9%; p = 0.0023) and ANCHOR (-12.1%; p <0.0001), along with significant increases of >500% in eicosapentaenoic acid levels in plasma and red blood cells (all p <0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]-Intervention Trial (REDUCE-IT) cardiovascular outcomes study.

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Section: Discussionmentioning

confidence: 99%

Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials)

Mosca

Ballantyne

Bays

et al. 2017

The American Journal of Cardiology

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“…Additionally, the animals showed no variation in weight gain and in food intake among diet treatments although D. vlkianum -treated animals had additional caloric intake from the microalgae supplement. It has been suggested that EPA rich diets might have strong effects on body weight reduction due to increased energy expenditure [ 17 ], which, taking into account the D. vlkianum richness in EPA, could explain the absence of body weight gain in regard to the caloric intake. One may argue that non-absorption of ingested microalgae-biomass is a reasonable explanation of the unchanged body weight.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Marine Microalga Diacronema vlkianum Biomass Fatty Acid Assimilation in Wistar Rats

et al. 2017

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Diacronema vlkianum is a marine microalgae for which supposed health promoting effects have been claimed based on its phytochemical composition. The potential use of its biomass as health ingredient, including detox-shakes, and the lack of bioavailability studies were the main concerns. In order to evaluate the microalgae-biomass assimilation and its health-benefits, single-dose (CD1-mice) studies were followed by 66-days repeated-dose study in Wistar rats with the highest tested single-dose of microalgae equivalent to 101 mg/kg eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA). Microalgae-supplementation modulated EPA and docosapentaenoic acid enrichment at arachidonic acid content expenditure in erythrocytes and liver, while increasing EPA content of heart and adipose tissues of rats. Those fatty acid (FA) changes confirmed the D. vlkianum-biomass FA assimilation. The principal component analyses discriminated brain from other tissues, which formed two other groups (erythrocytes, liver, and heart separated from kidney and adipose tissues), pointing to a distinct signature of FA deposition for the brain and for the other organs. The improved serum lipid profile, omega-3 index and erythrocyte plasticity support the cardiovascular benefits of D. vlkianum. These results bolster the potential of D. vlkianum-biomass to become a “heart-healthy” food supplement providing a safe and renewable source of bioavailable omega-3 FA.

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“…Recently, Ishida et al reported that, in hamsters fed a high-fat diet, DHA significantly increased the LDL-C levels, whereas EPA had no effect on the LDL-C levels. DHA, but not EPA, increased the plasma cholesterylester transfer protein (CETP) activity and decreased the LDL receptor expression in the liver 36) . These mechanisms may, at least partly, underlie the higher DHA/AA ratios found in obese patients with dyslipidemia compared to those without dyslipidemia in our study.…”

Section: Discussionmentioning

confidence: 99%

An Increase in the EPA/AA Ratio is Associated with Improved Arterial Stiffness in Obese Patients with Dyslipidemia

Itô

Satoh‐Asahara

Yamakage

et al. 2014

JAT

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Aim: Previous epidemiological studies demonstrated that the ratio of n-6 to n-3 polyunsaturated fatty acids is associated with cardiovascular diseases. We herein investigated whether the beneficial effect of highly purified eicosapentaenoic acid (EPA) on arterial stiffness is associated with changes in the ratio of polyunsaturated fatty acids, such as EPA, docosahexaenoic acid (DHA) and dihomo-γ-linolenic acid (DGLA), relative to arachidonic acid (AA), in obese Japanese patients with dyslipidemia. Methods: The EPA/AA, DHA/AA and DGLA/AA ratios were compared between obese patients with (n=94) and without (n= 31) dyslipidemia. Among the former group, 88 patients received either highly purified EPA treatment (1.8 g daily, n = 45) or treatment without EPA (control, n = 43). Results: At baseline, the ratios of DHA/AA and DGLA/AA were significantly (P＜0.05) higher in obese patients with dyslipidemia than in those without, while the EPA/AA ratio was similar between patients with and without dyslipidemia. EPA significantly reduced the hemoglobin A1c, total cholesterol, triglycerides, CRP, cardio-ankle vascular index (CAVI) (an index of arterial stiffness) and the DGLA/AA ratio relative to the control at three months after the treatment. On the other hand, EPA significantly increased the adiponectin level and EPA/AA ratio (P＜0.05). A multivariate regression analysis revealed that only age, an increase in the EPA/AA ratio and a decrease in the CRP level were significant determinants of a reduction of the CAVI by EPA. Conclusion: These findings suggest that EPA improves the arterial stiffness in association with an increase in the EPA/AA ratio and a decrease in inflammation in obese patients with dyslipidemia. J Atheroscler Thromb, 2014; 21:248-260.

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Distinct regulation of plasma LDL cholesterol by eicosapentaenoic acid and docosahexaenoic acid in high fat diet-fed hamsters: Participation of cholesterol ester transfer protein and LDL receptor

Cited by 36 publications

References 31 publications

Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials)

Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials)

Evaluation of Marine Microalga Diacronema vlkianum Biomass Fatty Acid Assimilation in Wistar Rats

An Increase in the EPA/AA Ratio is Associated with Improved Arterial Stiffness in Obese Patients with Dyslipidemia

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