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Abstract: Objective: Epidemiological studies suggest that consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFA) decreases the risk of heart failure. We assessed the effects of dietary supplementation with ω-3 PUFA from fish oil on the response of the left ventricle (LV) to arterial pressure overload. Methods: Male Wistar rats were fed a standard chow or a ω-3 PUFA-supplemented diet. After 1 week rats underwent abdominal aortic banding or sham surgery (n =9–12/group). LV function was assessed by echocardiography after 8 weeks. In addition, we studied the effect of ω-3 PUFA on the cardioprotective adipocyte-derived hormone adiponectin, which may alter the pro-growth serine–threonine kinase Akt. Results: Banding increased LV mass to a greater extent with the standard chow (31%) than with ω-3 PUFA (18%). LV end diastolic and systolic volumes were increased by 19% and 105% with standard chow, respectively, but were unchanged with ω-3 PUFA. The expression of adiponectin was up-regulated in adipose tissue, and the plasma adiponectin concentration was significantly elevated. Treatment with ω-3 PUFA increased total Akt protein expression in the heart, but decreased the fraction of Akt in the active phosphorylated form, and thus did not alter the amount of active phospho-Akt. Conclusion: Dietary supplementation with ω-3 PUFA attenuated pressure overload-induced LV dysfunction, which was associated with elevated plasma adiponectin. [Copyright &y& Elsevier]