Anselm Tintinu

AIMS: Clinical studies suggest that intake of omega-3 polyunsaturated fatty acids (omega-3 PUFA) may lower the incidence of heart failure. Dietary supplementation with omega-3 PUFA exerts metabolic and anti-inflammatory effects that could prevent left ventricle (LV) pathology; however, it is unclear whether these effects occur at clinically relevant doses and whether there are differences between omega-3 PUFA from fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and vegetable sources [alpha-linolenic acid (ALA)]. METHODS AND RESULTS: We assessed the development of LV remodelling and pathology in rats subjected to aortic banding treated with omega-3 PUFA over a dose range that spanned the intake of humans taking omega-3 PUFA supplements. Rats were fed a standard food or diets supplemented with EPA+DHA or ALA at 0.7, 2.3, or 7% of energy intake. Without supplementation, aortic banding increased LV mass and end-systolic and -diastolic volumes. ALA supplementation had little effect on LV remodelling and dysfunction. In contrast, EPA+DHA dose-dependently increased EPA and DHA, decreased arachidonic acid in cardiac membrane phospholipids, and prevented the increase in LV end-diastolic and -systolic volumes. EPA+DHA resulted in a dose-dependent increase in the anti-inflammatory adipokine adiponectin, and there was a strong correlation between the prevention of LV chamber enlargement and plasma levels of adiponectin (r = -0.78). Supplementation with EPA+DHA had anti-aggregatory and anti-inflammatory effects as evidenced by decreases in urinary thromboxane B(2) and serum tumour necrosis factor-alpha. CONCLUSION: Dietary supplementation with omega-3 PUFA derived from fish, but not from vegetable sources, increased plasma adiponectin, suppressed inflammation, and prevented cardiac remodelling and dysfunction under pressure overload conditions.

Coronary disease is reduced by intake of the ω-3 polyunsaturated fatty acids (ω-3PUFA) EPA and DHA. Recent evidence suggest EPA+DHA may also prevent development of heart failure. We previously showed that intake of fish oil rich in EPA+DHA up-regulates expression and plasma levels of adiponectin, a cardioprotective adipose-derived hormone. We examined the effects of dietary EPA+DHA on plasma adiponectin levels and development of left ventriclular (LV) dysfunction and remodeling in response to pressure overload induced by abdominal aorta banding. Rats were fed either a standard chow or diets supplemented with EPA+DHA from fish oil at 0.7%, 2.3% or 7% of energy intake. LV volumes were measured by echo. On the standard diet banding increased LV mass by 38%, LV end diastolic volume by 29%, and end diastolic volume by 101% compared to sham (p<0.05). EPA+DHA supplementation increased plasma adiponectin concentration in a dose dependent manner (see Fig. ), and prevented the increases in LV end diastolic volume and end systolic volume (p<0.05). Adiponectin levels were negatively correlated with LV end systolic and diastolic volumes (r=−0.78 and −0.71, respectively; p<0.001). The protective effect of adiponectin has been linked to AMPK activation and/or inhibition of pro-growth Akt, however there were no differences in AMPK or Akt activation by western blot. A parallel series of rats were fed with α-linolenic acid, a ω-3PUFA from flaxseed, over a similar dose range, and showed no increase in adiponectin or prevention of LV pathology. In conclusion, supplementation with EPA+DHA prevented LV remodeling and dysfunction, which was strongly associated with an elevation in plasma adiponectin.