Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China.
J Nutr. 2013 Aug;143(8):1331-9. doi: 10.3945/jn.113.176255. Epub 2013 Jun 5.
Proinflammatory cytokines play a key role in the pathophysiology of muscle atrophy. In addition, n3 polyunsaturated fatty acids (PUFAs) exert an inhibitory effect on proinflammatory cytokines affecting many inflammatory diseases. We hypothesized that dietary supplementation of fish oil could attenuate lipopolysaccharide (LPS)-induced muscle atrophy. Weanling pigs were used in a 2 × 2 factorial design and the main factors included diet (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline). After 21 d of treatment with either fish oil or corn oil, pigs received an i.p. injection of either saline or LPS. At 4 h postinjection, blood and muscle samples were obtained. Fish oil led to enrichment of eicosapentaenoic acid, docosahexaenoic acid, and total n3 PUFAs in muscles. Fish oil increased muscle protein mass, indicated by a higher protein:DNA ratio in gastrocnemius and longissimus dorsi (LD) muscles. In addition, fish oil increased Akt1 mRNA abundance and decreased Forkhead Box O (FOXO) 1 and FOXO4 mRNA abundance. Fish oil also increased phosphorylation of Akt and FOXO1 in gastrocnemius and LD muscles. Fish oil decreased the mRNA abundance of muscle atrophy F-box (MAFbx) and muscle RING finger 1 in gastrocnemius and LD muscles. Moreover, fish oil reduced the plasma tumor necrosis factor (TNF) α, muscle TNFα, and prostaglandin E2 concentrations, and muscle TNFα and cyclooxygenase 2 (COX2) mRNA abundance. Finally, fish oil downregulated the mRNA abundance of muscle toll-like receptor (TLR4) and its downstream signaling molecules [myeloid differentiation factor 88 (MyD88), TNFα receptor-associated factor 6 (TRAF6), and NF-κB p65], and nucleotide-binding oligomerization domain protein (NOD1), NOD2, and their adaptor molecule [receptor-interacting serine/threonine-protein kinase 2 (RIPK2)]. These results indicate fish oil may suppress muscle proinflammatory cytokine production via regulation of TLR and NOD signaling pathways and therefore improve muscle protein mass, possibly through maintenance of Akt/FOXO signaling.
促炎细胞因子在肌肉萎缩的病理生理学中发挥关键作用。此外，n3 多不饱和脂肪酸 (PUFA) 对影响许多炎症性疾病的促炎细胞因子具有抑制作用。我们假设，鱼油的饮食补充可能会减弱脂多糖 (LPS) 诱导的肌肉萎缩。我们使用 2×2 析因设计，主要因素包括饮食（5%玉米油或 5%鱼油）和免疫挑战（LPS 或盐水）。在用鱼油或玉米油治疗 21 天后，猪接受腹腔内注射盐水或 LPS。注射后 4 小时，采集血液和肌肉样本。鱼油导致二十碳五烯酸、二十二碳六烯酸和总 n3PUFA 在肌肉中的富集。鱼油增加了肌肉蛋白质量，表现为比目鱼肌和腰大肌的蛋白质：DNA 比值更高。此外，鱼油增加了 Akt1 mRNA 的丰度，降低了 Forkhead Box O (FOXO) 1 和 FOXO4 mRNA 的丰度。鱼油还增加了比目鱼肌和腰大肌中 Akt 和 FOXO1 的磷酸化。鱼油降低了比目鱼肌和腰大肌中肌肉萎缩 F 盒 (MAFbx) 和肌肉 RING 指蛋白 1 的 mRNA 丰度。此外，鱼油降低了血浆肿瘤坏死因子 (TNF) α、肌肉 TNFα 和前列腺素 E2 浓度，以及肌肉 TNFα 和环氧化酶 2 (COX2) mRNA 丰度。最后，鱼油下调了肌肉 Toll 样受体 (TLR4) 及其下游信号分子 [髓样分化因子 88 (MyD88)、肿瘤坏死因子受体相关因子 6 (TRAF6) 和 NF-κB p65] 和核苷酸结合寡聚化结构域蛋白 (NOD1)、NOD2 及其衔接分子 [受体相互作用丝氨酸/苏氨酸蛋白激酶 2 (RIPK2)] 的 mRNA 丰度。这些结果表明，鱼油可能通过调节 TLR 和 NOD 信号通路抑制肌肉促炎细胞因子的产生，从而改善肌肉蛋白质量，可能通过维持 Akt/FOXO 信号。
