Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-κB activation: From cells to bed rest to astronauts

Abstract

NF-κB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption—significant concerns for astronauts. NF-κB activation is inhibited by eicosapentaenoic acid (EPA), but the influence of this omega-3 fatty acid on the effects of weightlessness are unknown. We report here cellular, ground analogue, and spaceflight findings. We investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-κB ligand (RANKL) and on activation of NF-κB by tumor necrosis factor α (TNF-α) or exposure to modeled weightlessness. EPA (50 µM for 24 hours) inhibited RANKL-induced differentiation and decreased activation of NF-κB induced by 0.2 µg/mL of TNF-α for 30 minutes or by modeled weightlessness for 24 hours (p < .05). In human studies, we evaluated whether NF-κB activation was altered after short-duration spaceflight and determined the relationship between intake of omega-3 fatty acids and markers of bone resorption during bed rest and the relationship between fish intake and bone mineral density after long-duration spaceflight. NF-κB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids) was associated with reduced loss of bone mineral density after flight (p < .05). Also supporting the cell study findings, a higher intake of omega-3 fatty acids was associated with less N-telopeptide excretion during bed rest (Pearson r = –0.62, p < .05). Together these data provide mechanistic cellular and preliminary human evidence of the potential for EPA to counteract bone loss associated with spaceflight. © 2010 American Society for Bone and Mineral Research