Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation: from cells to bed rest to astronauts.
NF-kappaB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption-significant concerns for astronauts. NF-kappaB 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-kappaB ligand (RANKL) and on activation of NF-kappaB by tumor necrosis factor alpha (TNF-alpha) or exposure to modeled weightlessness. EPA (50 microM for 24 hours) inhibited RANKL-induced differentiation and decreased activation of NF-kappaB induced by 0.2 microg/mL of TNF-alpha for 30 minutes or by modeled weightlessness for 24 hours (p < .05). In human studies, we evaluated whether NF-kappaB 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-kappaB 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.
Zwart
Sara R
SR
Universities Space Research Association, NASA Johnson Space Center, Human Adaptation and Countermeasures Division, Houston, TX 77058, USA. sara.zwart-1@nasa.gov
Pierson
Duane
D
Mehta
Satish
S
Gonda
Steve
S
Smith
Scott M
SM
D000328:Adult; D000818:Animals; D001510:Bed Rest / Q000009:adverse effects*; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D053245:RANK Ligand / Q000494:pharmacology; D013026:Space Flight; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014893:Weightlessness / Q000009:adverse effects*
D015525:Fatty Acids, Omega-3; D016328:NF-kappa B; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D015118:Eicosapentaenoic Acid