Little, Sarah Elizabeth (2020-04). Dietary Modulation of Inflammation-Mediated Effects on Skeletal Biology. Doctoral Dissertation.
Chronic inflammation leads to bone loss and fragility. Signaling of proinflammatory cytokines, like tumor necrosis factor-alpha (TNF?), is integral to promote bone resorption. Dietary modulation of pro-inflammatory cytokines is a therapeutic target for disorders associated with chronic inflammation, including space-relevant radiation exposure and diet-induced obesity (DIO), though much remains poorly understood. As such, we seek to investigate whether an anti-inflammatory diet can reduce radiation-mediated damage and whether diet and microbiota supplementation can reverse the negative effects of a pro-inflammatory diet on bone. We assessed the efficacy of a diet high in omega-3 fatty acids in mitigating radiation-induced bone loss via reductions in inflammatory cytokines in bone osteocytes and serum. Interestingly, we failed to detect a negative impact of radiation exposure on cancellous and cortical bone parameters, despite increased serum levels of TNF? with radiation exposure. A high omega-3 fatty acid diet mitigated the radiation-induced increase in serum levels of TNF?. High omega-3-fed mice exhibited improved cancellous and cortical microarchitecture and geometry at 8 weeks post-exposure to 56Fe and ? radiation, with improvements occurring at higher radiation doses. Though we did not detect the expected impact of radiation on bone parameters, mitigation of inflammatory cytokines via an anti-inflammatory diet resulted in modest improvements in bone outcomes and reduced systemic inflammation, as assessed by serum TNF?. In the second experiment, we assessed whether altering dietary intake from a high fat, high sugar (HFS) to a low-fat diet, with or without fecal microbial transplants (FMT) rescued bone integrity in diet-induced obesity. Contrary to our expectations, HFS feeding promoted bone anabolism and improved femur structural properties with no detectable inflammatory impact, suggesting exercise is protective against systemic inflammation. HFS-fed mice did not improve femur material properties, nor femoral neck strength, suggesting improved bone quantity, but not quality. FMT treatment exhibited a differential impact on femur material properties that should be investigated further. Together, our results suggest that dietary modulation of inflammatory cytokines may be effective against negative bone impacts related to systemic inflammation; however, in the context of chronic inflammation and DIO, exercise appears to outweigh the detrimental impact of HFS-induced inflammation on bone.