Oxylipin status, before and after LC n-3 PUFA supplementation, has little relationship with skeletal muscle biology in older adults at risk of sarcopenia. (February 2023)

• Record Type: Journal Article
• Authors: de Marco Castro, E.; Kampschulte, N.; Murphy, C.H.; Schebb, N.H.; Roche, H.M.
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 189(2023)
• Publication Date: 2023-02
• Subjects: LC n-3 PUFA -- LC n-6 PUFA -- EPA -- DHA -- ARA -- Skeletal muscle -- Oxylipins -- Sarcopenia; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2022.102531
• Languages: English
• ISSNs: 0952-3278

Abstract

Highlights: At baseline, certain n- 9 and n- 6 hydroxy‑PUFA derived oxylipins [i.e., 5- and 12-HETrE, and 5- 11- and 16-HETE] were negatively correlated with markers of skeletal muscle mass and strength in older adults at risk of sarcopenia. LC n -3 PUFA shifted erythrocyte membrane FA composition and oxylipin profile, wherein higher concentrations of EPA and DHA derived oxylipins, and lower levels of n -9 and n -6 PUFA (especially ARA) derived oxylipins were present in plasma. However, LC n -3 PUFA supplementation did not impact skeletal muscle mass or strength. Oxylipin changes with supplementation were closely correlated to their parent PUFA not only for EPA as previously described but also for most n -3 and n -6 PUFA. LC n- 3 PUFA-driven EPA and DHA derived oxylipin changes depended on EPA and DHA baseline status. Abstract: Introduction: 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. Materials and methods: 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. Results: 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. Discussion and conclusion: 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.