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

Abstract

Increased dietary LCn-3PUFA (long-chain n-3 polyunsaturated fatty acid) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn-3PUFAs elicit similar anabolic effects in healthy individuals. To answer this question, we evaluated the effect of 8 weeks of LCn-3PUFA supplementation (4 g of Lovaza®/day) in nine 25-45-year-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 (mammalian target of rapamycin)/p70S6K (p70 S6 kinase) signalling pathway during basal post-absorptive conditions and during a hyperinsulinaemic-hyperaminoacidaemic 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 and the phospho-mTOR (Ser2448) and phospho-p70S6K (Thr389) levels increased by ∼50%; all P<0.05]. In addition, the muscle protein concentration and the protein/DNA ratio (i.e. muscle cell size) were both greater (P<0.05) after LCn-3PUFA supplementation. We conclude that LCn-3PUFAs have anabolic properties in healthy young and middle-aged adults.

Figures

Figure 1. Muscle protein concentration, cell size, and capacity for protein synthesis

Muscle alkali soluble protein concentration (A), the protein-to-DNA ratio in muscle (an index of cell size; B), and the RNA-to-DNA ratio (an index for the cell capacity for protein synthesis; C) before and after eight weeks of long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation. Values are means ± SEM. a Value significantly (P < 0.05) different from corresponding value before LCn-3PUFA supplementation. The difference in the RNA-to-DNA ratio did not reach statistical significance (P = 0.13).

Figure 2. Muscle protein fractional synthesis rates

Muscle protein fractional synthesis rates (FSR) during basal, post-absorptive conditions and during the hyperinsulinemic-hyperaminoacidemic clamp procedure before and after eight weeks of long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation. Values are means ± SEM. ANOVA revealed a significant main effect of hyperinsulinemia-hyperaminoacidemia (P a Value significantly different (P < 0.01) from corresponding basal value. b Value significantly (P < 0.01) different from corresponding value before LCn-3PUFA supplementation.

Figure 3. Skeletal muscle anabolic signalling responses

Concentrations (arbitrary units) of phosphorylated AktThr308 (A), mTORSer2448 (B), p70s6kThr389 (C), and eEF2Thr56 (D) during basal, postabsorptive conditions and during the hyperinsulinemic-hyperaminoacidemic clamp procedure before and after eight weeks of long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation. Values are means ± SEM or medians (horizontal lines) with quartiles (boxes) and minimum and maximum values (vertical lines). a,b For AktThr308, ANOVA revealed a main effect of hyperinsulinemia-hyperaminoacidemia (P = 0.042) and LCn-3PUFA (P = 0.023) but no interaction (P = 0.976). For mTORSer2448 and p70s6kThr389, ANOVA revealed a main effect of hyperinsulinemia-hyperaminoacidemia (P < 0.01) and a significant interaction (P < 0.05); Tukey post-hoc analysis located the specific differences as follows: c value significantly different from corresponding basal value (P < 0.01); d value significantly different from corresponding value before LCn-3PUFA supplementation (P < 0.05). e value significantly different from corresponding basal value (P < 0.05).