6. 6. Clin Sci (Lond). 2011 Sep; 121(6): 267–278.

Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperaminoacidemia-hyperinsulinemia in healthy young and middle aged men and women

Gordon I. Smith,¹ Philip Atherton,² Dominic N. Reeds,¹ B. Selma Mohammed,¹ Debbie Rankin,² Michael J. Rennie,² and Bettina Mittendorfer¹

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Abstract

Increased dietary long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn-3PUFA elicit similar anabolic effects in healthy individuals. To answer this question we evaluated the effect of 8 weeks of LCn-3PUFA supplementation (4 g·d⁻¹ of Lovaza®) in nine 25–45 y old healthy subjects on the rate of muscle protein synthesis (by using stable isotope labelled tracer techniques) and the activation (phosphorylation) of elements of the mTOR-p70s6k pathway during basal, postabsorptive conditions and during a hyperinsulinemic-hyperaminoacidemic clamp. We also measured the concentrations of protein, RNA, and DNA in muscle to obtain indices of the protein synthetic capacity, translational efficiency and cell size. Neither the basal muscle protein fractional synthesis rate nor basal signalling element phosphorylation changed in response to LCn-3PUFA supplementation but the anabolic response to insulin and amino acid infusion was greater after LCn-3PUFA (i.e., the muscle protein fractional synthesis rate during insulin and amino acid infusion increased from 0.062 ± 0.004 to 0.083 ± 0.007 %·h⁻¹ and the phospho mTOR^Ser2448 and p70s6k^Thr389 concentrations increased by ~50%; all P < 0.05). In addition, the muscle protein concentration and the protein-to-DNA ratio (i.e., muscle cell size) were both greater (P < 0.05) after LCn-3PUFA supplementation. We conclude that LCn-3PUFA have anabolic properties in healthy young and middle aged adults. Increased dietary long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn-3PUFA elicit similar anabolic effects in healthy individuals. To answer this question we evaluated the effect of 8 weeks of LCn-3PUFA supplementation (4 g·d⁻¹ of Lovaza®) in nine 25–45 y old healthy subjects on the rate of muscle protein synthesis (by using stable isotope labelled tracer techniques) and the activation (phosphorylation) of elements of the mTOR-p70s6k pathway during basal, postabsorptive conditions and during a hyperinsulinemic-hyperaminoacidemic clamp. We also measured the concentrations of protein, RNA, and DNA in muscle to obtain indices of the protein synthetic capacity, translational efficiency and cell size. Neither the basal muscle protein fractional synthesis rate nor basal signalling element phosphorylation changed in response to LCn-3PUFA supplementation but the anabolic response to insulin and amino acid infusion was greater after LCn-3PUFA (i.e., the muscle protein fractional synthesis rate during insulin and amino acid infusion increased from 0.062 ± 0.004 to 0.083 ± 0.007 %·h⁻¹ and the phospho mTOR^Ser2448 and p70s6k^Thr389 concentrations increased by ~50%; all P < 0.05). In addition, the muscle protein concentration and the protein-to-DNA ratio (i.e., muscle cell size) were both greater (P < 0.05) after LCn-3PUFA supplementation. We conclude that LCn-3PUFA have anabolic properties in healthy young and middle aged adults.