背景:氧化脂素通过长链多不饱和脂肪酸(LCPUFA)的氧合内源性形成。几种氧化脂素是高度生物活性的分子,并且被认为是体内LC-PUFA代谢的关键介质。然而,关于氧化脂素是否介导骨骼肌质量和功能的改变知之甚少。这项研究的目的是确定处于肌肉减少症风险的健康老年人的羟脂素谱与骨骼肌生物学之间是否存在关系,并确定这种变化是否响应于LCn-3PUFA补充。
方法:这项探索性研究调查了LCn-3,n-6和n-9PUFA衍生的氧化脂素与肌肉生物学标志物之间的基线相关性。为此,79游离的浓度(即,通过液相色谱-质谱(LC-MS)对人血浆中的非酯化)氧化脂素进行定量,并与NUTRIMAL研究干预前获得的表型结局进行回顾性关联(n=49).检查基线关系后,补充(LCn-3PUFA或由高油酸向日葵和玉米油制成的等能量对照)的潜在作用是通过关联氧化脂素浓度的变化和骨骼肌生物学标志物的变化来评估的。还检查了干预前后氧化脂素与其父母PUFA之间的关系。
结果:在基线时,蜂蜜酸的羟基产物(n-9PUFA),5-HETrE,与表型参数阑尾瘦质量指数(ALMI)呈负相关(p=0.003,r=-0.41),骨骼肌质量指数(SMMI)(p=0.001,r=-0.46),握力(HGS)(p<0.001,r=0.48)和等距膝盖伸展(p<0.001,r=-0.48)。同样,LCn-6PUFA羟基-PUFA与HGS呈负相关(即,12-HETrE,p=0.002,r=-0.42,以及5-和11-HETE,p=0.006,r=-0.47和p<0.001,r=-0.50),单腿站立时间(即,12-HETrE,p=0.006,r=-0.39和16-HETE,p=0.002,r=-0.43),和五次坐立测试(FTST)性能(16-HETE,p=0.006,r=0.39),并与步态速度呈正相关(即,12-HETrE,p=0.007,r=0.38和16-HETE,p=0.006,r=0.39)。LCn-3PUFA的补充增加了二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)衍生的氧化脂素,并减少了n-6PUFA衍生的氧化脂素。在LCn-3PUFA或安慰剂组中,骨骼肌质量和力量的参数均无明显变化。血浆氧化脂素浓度的变化与其母体PUFA的变化密切相关,在红细胞膜中评估,但与骨骼肌参数的任何变化无关。
结论:在基线时,状态n-9(5-HETrE)和n-6PUFA衍生物[12-HETrE,和5-,11-和16-HETE],但不是n-3PUFA衍生的氧化脂素,与不良的骨骼肌健康参数相关(即,质量和强度)。然而,当关联前后时间点的相对变化时,这些相关性不再存在.需要一个独立的队列验证来进一步探索基线相关性。需要进一步的研究来评估LCn-3PUFA可能影响肌肉生物学的其他生物学机制。
Oxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC n-3 PUFA supplementation.
This exploratory study investigated the baseline correlations between LC n-3, n-6 and n-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (n = 49). After examining the baseline relationship, the potential effect of supplementation (LC n-3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined.
At baseline, the hydroxy product of mead acid (n-9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (p = 0.003, r=-0.41), skeletal muscle mass index (SMMI) (p = 0.001, r=-0.46), handgrip strength (HGS) (p<0.001, r = 0.48) and isometric knee extension (p<0.001, r=-0.48). Likewise, LC n-6 PUFA hydroxy‑PUFA were negatively correlated to HGS (i.e., 12-HETrE, p = 0.002, r=-0.42, and 5- and 11-HETE, p = 0.006, r=-0.47 and p<0.001, r=-0.50 respectively), single leg stand time (i.e., 12-HETrE, p = 0.006, r=-0.39 and 16-HETE, p = 0.002, r=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, p = 0.006, r = 0.39), and positively correlated to gait speed (i.e., 12-HETrE, p = 0.007, r = 0.38 and 16-HETE, p = 0.006, r = 0.39). LC n-3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced n-6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC n-3 PUFA or placebo groups. Changes in plasma oxylipins concentrations were closely related to changes in their parent PUFA, assessed in the erythrocyte membrane, but were not associated with any changes in skeletal muscle parameters.
At baseline, the status n-9 (5-HETrE) and n-6 PUFA derivates [12-HETrE, and 5-, 11- and 16-HETE], but not n-3 PUFA derived oxylipins, were associated with poor skeletal muscle health parameters (i.e., mass and strength). However, these correlations were no longer present when correlating relative changes from pre to post timepoints. An independent cohort validation is needed to explore baseline correlations further. Further research is warranted to assess other biological mechanisms by which LC n-3 PUFA might affect muscle biology.