Abstract

Obesity is a widespread epidemic that increases the risk for several metabolic diseases. Despite several beneficial health effects of eicosapentaenoic acid (C20:5n-3, EPA), previous studies have used very high doses of EPA. In this study, dose-dependent effects of EPA on metabolic outcomes were determined in diet-induced obese mice. We used B6 male mice, fed high-fat diet (HF, 45% kcal fat) or HF diet supplemented with 9, 18, and 36 g/kg of EPA-enriched fish oil for 14 weeks. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. Only mice fed 36 g/kg of EPA significantly (p < 0.05) lowered body weight, fat content and epididymal fat pad weight, compared to HF. Both 18 and 36 g/kg doses of EPA significantly increased glucose clearance and insulin sensitivity, compared to HF or 9 g/kg of EPA. Locomotor activity was significantly increased with both 18 and 36 g/kg doses of EPA. Interestingly, all doses of EPA compared to HF, significantly increased energy expenditure and oxygen consumption and significantly reduced serum insulin, leptin, and triglycerides levels. These results demonstrate weight- and adiposity-independent metabolic benefits of EPA, at doses comparable to those currently used to treat hypertriglyceridemia.

Highlights

  • The growing prevalence of obesity across the world increases risk of metabolic and cardiovascular diseases, and obesity is recognized as a disease of epidemic proportions [1,2]

  • We have previously reported that mice fed a high-fat diet supplemented with EPA36 (36 g eicosapentaenoic acid (EPA)/kg diet) displayed an improved overall metabolic profile, independent of obesity [22]

  • Food intake was measured per mice weekly, and it was comparable between HF, EPA9, EPA18, and EPA36 throughout the feeding period (Figure 1A)

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Summary

Introduction

The growing prevalence of obesity across the world increases risk of metabolic and cardiovascular diseases, and obesity is recognized as a disease of epidemic proportions [1,2]. It increases risk of co-morbidities including type II diabetes, insulin resistance, heart diseases and some cancers [3]. Dietary energy restriction and increased physical activity are recommended lifestyle strategies for reducing obesity. These are efficient, but compliance is an issue [6]. We are interested in long-chain ω3 polyunsaturated fatty acids (PUFA)

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