Concentration of Serum Lipids and Aortic Lesion Size in Female and Male Apo E-Deficient Mice Fed Docosahexaenoic Acid

Abstract

Apolipoprotein (apo) E-deficient mice were fed an atherogenic diet with either 1% ethyl ester docosahexaenoic acid (DHA) or safflower oil (SO) as a source of linoleic acid for 8 week. Both genders fed DHA had higher proportions of eicosapentaenoic acid and DHA, and lower proportions of linoleic and arachidonic acids in the liver and serum phospholipids than those fed SO. Males fed DHA had greater liyer weight and tended to haye higher concentrations of serum lipids and liyer cholesterol than those fed SO, and there were opposite trends in fema]es. Dietary fats and gender led to no significant effect on lesion sizes in aortic arch and thoracic plus abdominal aorta. These results indicate that the interactiye action of sex-related factor(s) with dietary polyunsaturated fatty acids is inyolyed in metabolic changes of serum lipids in apoEdeficient mice, and addition ef DHA, conipared with addition of SO, is not effective to abollsh the atherosclerosis in this animal model.

Effect of n-3 fatty acids on serum lipid levels and hepatic fatty acid metabolism in BALB/c.KOR-Apoeshl mice deficient in apolipoprotein E expression

“…In contrast to previous observations [2,24], fish oil and n-3 fatty acid ethyl esters caused great decreases in serum cholesterol, triacyglycerol, and phospholipid levels in apoEdeficent mice in the present study. The levels in the animals fed fish oil and n-3 fatty acid ethyl esters dropped to less than 30% and 50%, respectively, of the values in the animals fed palm oil.…”

“…We hypothesized that apoE expression is required for n-3 fatty acid-dependent regulation of hepatic fatty acid metabolism, and a disturbance in the regulation of the metabolic pathway may account for the failure of fish oil to reduce serum lipid levels in apoE-knockout (Apoe tm1Unc ) mice observed in previous studies [2,24]. To address this point, we used an alternative apoE-deficient model (BALB/ c.KOR-Apoe shl mice) that we have developed [22,23].…”

“…Compared to both sunflower and coconut oils, fish oil caused more than a 4-fold increase in plasma triacylglycerol concentrations in the apoE-knockout mice despite that it decreased plasma cholesterol and triacylglycerol concentrations in the wild-type mice. Adan et al [24] showed that DHA ethyl ester caused a slight decrease in serum cholesterol levels in female apoE-knockout mice. However, it was ineffective in reducing this parameter in male apoE-knockout mice.…”

“…Previous findings [2,24] that dietary n-3 fatty acids are rather irrelevant in reducing serum lipid levels in apoEknockout (Apoe tm1Unc ) mice possibly indicated that apoE expression is required for n-3 fatty acid-dependent regulation of hepatic fatty acid metabolism or the basal metabolic activities of fatty acid oxidation and synthesis are too low in apoE-deficient mice to affect hepatic lipoprotein production. However, a study to examine the effect of n-3 fatty acids on hepatic fatty acid oxidation and synthesis in apoEdeficient mice has been lacking.…”

Eicosapentaenoic Acid and Docosahexaenoic Acid Regulate Modified LDL Uptake and Macropinocytosis in Human Macrophages

“…In particular, these fish oil derived n-3 PUFA have been shown to be atheroprotective in different mouse models of the disease [12][13][14][15][16], to reverse defective efferocytosis of apoptotic cells in obese mice [17], to enhance atherosclerotic plaque stability in humans awaiting carotid endarterectomy [18] and to be effective in reducing the risk of cardiac mortality [19,20]. Nevertheless, despite this evidence, other studies have contradicted some of these results [21][22][23] although this could be linked to background levels of n-6 PUFA since these can affect the efficacy of n-3 PUFA in atheroprotection [24] and since lowering the n-6:n-3 PUFA ratio in ApoE -/-mice reduces atherosclerotic plaque development [16]. Some of the atheroprotective effects of n-3 PUFA in mice have been shown to involve changes in macrophage function [12,17] and a recent study found that EPA, delivered from n-3 PUFA ethyl esters, reduced foam cell accumulation in advanced human carotid plaques [25] suggesting that n-3 PUFA not only target macrophage activity but also foam cell formation.…”