Br J Nutr. , 2020., 123(8):859‐869.

Effect of Flaxseed Oil on Muscle Protein Loss and Carbohydrate Oxidation Impairment in a Pig Model After Lipopolysaccharide Challenge

Kang P, Wang Y, Li X, et al.

Abstract

Flaxseed oil is rich in α-linolenic acid (ALA), which is the metabolic precursor of EPA and DHA. The present study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model.

Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5 % maize oil v. 5 % flaxseed oil) and LPS challenge (saline v. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 μg/kg body weight LPS or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 PUFA contents, protein:DNA ratio and pyruvate dehydrogenase complex quantity in muscles (P < 0·05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) 2 and their downstream signalling molecules in muscles and decreased plasma concentrations of TNF-α, IL-6 and IL-8, and mRNA expression of TNF-α, IL-1β and IL-6 (P < 0·05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated protein kinase B (Akt) 1:total Akt1 and phosphorylated Forkhead box O (FOXO) 1:total FOXO1 and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1 and pyruvate dehydrogenase kinase 4 in muscles (P < 0·05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of the TLR4/NOD and Akt/FOXO signalling pathways.

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Key Points

The hypothesis was that flaxseed oil could reduce muscle protein loss and play an important role in attenuating carbohydrate oxidation impairment induced by LPS challenge. Flaxseed oil inclusion increased ALA, EPA and total n-6:n-3 PUFA contents. In the present study, it was found that flaxseed oil supplementation could optimise n6:n3 ratios compared with maize oil.

Muscle atrophy is generally associated with excessive loss of muscle protein. Plasma BUN concentration is an indirect index to reflect muscle protein degradation. Flaxseed oil inclusion decreased BUN content in blood, suggesting that flaxseed oil attenuated LPS-induced muscle atrophy by reducing protein degradation in both normal and stress status. Flaxseed oil inclusion prevented the reduction of protein:DNA ratio after LPS challenge, indicating that flaxseed oil could increase muscle protein mass to prevent muscle atrophy induced by LPS. Consistent with improved muscle protein mass (increased protein:DNA ratio) and carbohydrate metabolism (increased PDC quantity), flaxseed oil decreased plasma pro-inflammatory TNF-α, IL-6 and IL-8 concentrations and muscle TNF-α, IL-6, IL-1β,and TLR4, NOD2 and their downstream signalling molecules mRNA expression after LPS injection. Previous studies have shown that proinflammatory cytokines can elevate catabolic hormones such as cortisol and glucagon. Cortisol is an inhibitor of muscle protein synthesis. In this study, flaxseed oil reduced plasma cortisol content, indicating that flaxseed oil could attenuate protein degradation through decreasing plasma cortisol content after LPS challenge. In summary, diet supplemented with flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment. These beneficial effects of flaxseed oil on muscles might be associated with regulating the TLR4/ NOD and Akt/FOXO signalling pathways.