Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

Vlijmen, Bart J.M. van; Mensink, Ronald P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, Marten H.; Havekes, Louis M.

doi:10.1016/s0022-2275(20)32542-6

Cited by 30 publications

(3 citation statements)

References 30 publications

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“…Our current findings are consistent with another study in our laboratory that showed that remnant-size n-3 tridocosahexaenoin emulsions are cleared faster than remnant-size n-6 triolein emulsions and trioctanion/triolein (1/1, w/w) emulsions () . Also, n-3 TG reduces plasma TG levels in rat and mice by accelerating chylomicron and VLDL particle clearance ( , ), an effect not associated with differences in lipolysis (). In humans, addition of 10% fish oil TG to MCT/LCT intravenous lipid emulsions enhanced elimination of infused TG, a difference not related to a higher rate of hydrolysis, but rather to a more efficient uptake of emulsion particles ().…”

Section: Discussionsupporting

confidence: 92%

Omega-3 Triglycerides Modify Blood Clearance and Tissue Targeting Pathways of Lipid Emulsions

Seo

Al-Haideri

et al. 2002

Biochemistry

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Omega-3-rich (n-3) triglycerides (TG) are increasingly recognized as having modulating roles in many physiological and pathological conditions. We questioned whether the catabolism of lipid emulsions would be changed after enrichment with fish oil (n-3) TG as compared to enrichment with omega-6-rich soy oil (n-6) TG. Phospholipid-stabilized emulsions of n-3 TG and n-6 TG were labeled with [(3)H]cholesteryl oleoyl ether and administered by bolus injection to wild-type (WT) mice, mice lacking the low-density lipoprotein receptor (LDL-R) (LDL-R -/-), and apolipoprotein E (apoE) knockout mice (apoE -/-). The effects of exogenous apoE, heparin, Triton WR 1339, and lactoferrin on catabolism of emulsions were also assayed. n-3 TG emulsions were cleared faster from blood and had different extrahepatic tissue targeting compared to n-6 TG emulsions. In apoE -/- and LDL-R -/- mice, blood clearance of n-6 TG emulsions slowed with decreased liver uptake, but no changes were observed in n-3 TG emulsion clearance and tissue uptake compared to WT mice. In WT mice, addition of exogenous apoE to the emulsion increased liver uptake of n-6 TG emulsions but had no impact on n-3 TG emulsions. Pre-injection of heparin increased and Triton WR 1339 and lactoferrin decreased blood clearance of n-6 TG emulsions with little or no effect on n-3 TG emulsions. Liver uptake of n-6 TG emulsions increased after heparin injection and decreased after Triton WR 1339 injection, but uptake of n-3 TG emulsions was not changed. These data show that the catabolism of n-3 TG emulsions and the catabolism of n-6 TG emulsions occur via very different mechanisms. Removal of chylomicron-sized n-6 TG emulsions is modulated by lipoprotein lipase (LPL), apoE, LDL-R, and lactoferrin-sensitive pathways. In contrast, clearance of chylomicron-sized n-3 TG emulsions relies on LPL to a very minor extent and is independent of apoE, LDL-R, and lactoferrin-sensitive pathways.

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Section: Discussionsupporting

confidence: 92%

Omega-3 Triglycerides Modify Blood Clearance and Tissue Targeting Pathways of Lipid Emulsions

Seo

Al-Haideri

et al. 2002

Biochemistry

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“…Numerous studies have documented the beneficial effects of n-3 FAs when added to the diet in the form of TG (i.e., n-3:TG). Certain studies in mice have documented the ability of n-3:TG to reduce plasma and liver lipid levels − , others have reported the ability of n-3:TG to increase insulin sensitivity , , while others have described the anti-inflammatory effects of n-3:TG, either in the liver − or in the adipose tissue , . Most of these studies used relatively high doses of FO (i.e., 10% or more FO by energy, equivalent to >3% en EPA + DHA), and virtually all of them substituted fat in the diet with n-3:TG, rather than adding n-3:TG to the diet in the form of a dietary supplement.…”

Section: Discussionmentioning

confidence: 99%

Dietary Krill Oil Supplementation Reduces Hepatic Steatosis, Glycemia, and Hypercholesterolemia in High-Fat-Fed Mice

Tandy¹,

Chung²,

Wat³

et al. 2009

J. Agric. Food Chem.

128

113

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Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids rather than in triglycerides. In the present study, we investigated the effects of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk + 0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4) HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO supplementation caused a significant reduction in liver wt (i.e., hepatomegaly) and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/- 5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by 20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34 +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These results demonstrate that dietary KO is effective in improving metabolic parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic value in patients with the metabolic syndrome and/or nonalcoholic fatty liver disease.

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“…The effects of dietary fish oil were tested in this hyperlipidemic mouse model (68). In contrast to the apoe y/y mouse, the APOE3L mouse seemed to be highly responsive to this treatment.…”

Section: Apoe3leiden Mouse Modelmentioning

confidence: 99%

Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice

Wouters

Shiri-Sverdlov²,

Gorp³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

Self Cite

136

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Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.

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Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

Cited by 30 publications

References 30 publications

Omega-3 Triglycerides Modify Blood Clearance and Tissue Targeting Pathways of Lipid Emulsions

Omega-3 Triglycerides Modify Blood Clearance and Tissue Targeting Pathways of Lipid Emulsions

Dietary Krill Oil Supplementation Reduces Hepatic Steatosis, Glycemia, and Hypercholesterolemia in High-Fat-Fed Mice

Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice

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