Abstract 1583: Eicosapentaenoic Acid Up-Regulates Adiponectin Expression in Peri-adventitial Adipose Tissue and Suppresses Atherosclerotic Lesion Formation in ApoE-Deficient Mice
Background: Accumulating evidence demonstrates that dietary intake of n-3 polyunsaturated fatty acids (PUFA) has beneficial effects on cardiovascular events through various mechanisms. We examined the effect of eicosapentaenoic acid (EPA), a major component of n-3 PUFA, on adiponectin expression and atherosclerosis development in ApoE-deficient mice. Adiponectin is a circulating adipose-derived cytokine that has anti-atherogenic and anti-inflammatory properties.
Methods and Results: Male five-week-old ApoE-deficient mice were orally fed a western-type diet including or not including 5% EPA (EPA group n=7, Control n=5) for 13 weeks. Fatty acid composition analysis of liver homogenates revealed that total tissue content of n-3 PUFA had markedly increased with oral administration of EPA.EPA increased triglyceride levels but had no significant effect on total or HDL cholesterol levels. Adiponectin mRNA expression was remarkably up-regulated by EPA in peri-adventitial and subcutaneous adipose tissues, but not in visceral tissue. Our in vitro mouse culture cell experiment confirmed that EPA significantly increased adiponectin secretion from differentiated 3T3L1 adipocytes (2.1 ± 0.34 vs. 1.4 ± 0.15 ng/ml, p<0.05). En face Sudan IV staining of aorta showed that EPA significantly suppressed development of atherosclerotic lesions (5.1 ± 1.2 vs. 18.7 ± 3.1%, p<0.01). The EPA group lesions had smaller lipid deposition (10.9 ± 5.3 vs. 20.4 ± 2.2%, p<0.05), thicker fibrous caps (3.6 ± 0.8 vs. 1.3 ± 0.2%, p<0.05) and less macrophage accumulation (14.7 ± 2.0 vs. 32.7 ± 4.1%, p<0.05).
Conclusions: EPA enhances adiponectin expression in selected adipose tissue and reduces and stabilizes atherosclerotic lesions. Enhanced adiponectin expression in peri-adventitial tissue may thus partly contribute to EPA’s anti-atherosclerotic effects.