Chronic inflammation leads to bone loss and fragility. Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα) consistently promote bone resorption. Dietary modulation of pro-inflammatory cytokines is an accepted therapeutic approach to treat chronic inflammation, including that induced by space-relevant radiation exposure. As such, these studies were designed to determine whether an anti-inflammatory diet, high in omega-3 fatty acids, could reduce radiation-mediated bone damage via reductions in the levels of inflammatory cytokines in osteocytes and serum. Lgr5-EGFP C57BL/6 mice were randomized to receive diets containing fish oil and pectin (FOP; high in omega-3 fatty acids) or corn oil and cellulose (COC; high in omega-6 fatty acids), then acutely exposed to 0.5 Gy 56Fe or 2.0 Gy gamma radiation. Mice fed the FOP diet exhibited consistent reductions in serum TNFα in the 56Fe, but not the gamma, experiment. The percentage osteocytes (%Ot) positive for TNFα increased in gamma exposed COC, but not FOP, mice. Minimal changes in %Ot positive for sclerostin were observed. FOP mice exhibited modest improvements in several measures of cancellous microarchitecture and volumetric bone mineral density (vBMD) post-exposure to 56Fe and gamma radiation. Reduced serum TNFα in FOP mice exposed to 56Fe was associated with either neutral or modestly positive changes in bone structural integrity. Collectively, these data are generally consistent with previous findings that dietary intake of omega-3 fatty acids may effectively mitigate systemic inflammation after acute radiation exposure and facilitate maintenance of BMD during spaceflight in humans.
Omega-3 Fatty Acid Modulation of Serum and Osteocyte Tumor Necrosis Factor Alpha in Adult Mice Exposed to Ionizing Radiation