Diet-induced obesity fails to prime tumour-associated neuroinflammation in mice with Lewis Lung Carcinoma.

As obesity rates rise throughout the world and, given that obesity increases cancer risk for many forms of cancer, we can expect the rates of comorbid obesity and cancer to also rise. While obesity increases cancer-related symptoms including fatigue, depression, and neuropathy, the mechanisms underlying this exacerbation are understudied. As cancer and obesity have both been associated with alterations in neuroinflammatory processes, we used a murine model to investigate the interaction between cancer and obesity-associated neuroinflammation. We hypothesized that diet-induced obesity would result in neuroinflammatory priming and exacerbate tumour-associated neuroinflammation. Across 3 experiments, we evaluated the effect of diet in both male and female C57BL6J mice and tested two different diet durations: (1) 9 weeks of 45% High-Fat Diet (HFD) in female mice, (2) 9 weeks of 45% HFD in male mice, and (3) 24 weeks of 45% HFD with 10% fructose water in male mice. Mice on HFD and Standard Diet (SD) were randomized to receive either an injection of Lewis Lung Carcinoma (LLC) cells or PBS vehicle subcutaneously into the flank. After tumors were allowed to grow for approximately 3 weeks, tissue was collected and proinflammatory cytokine expression was evaluated in the hippocampus and hypothalamus. Overall, our results indicate that while long-term HFD consumption led to poorer health outcomes (as measured by faster tumor growth, enhanced weight loss, and greater spleen weights), it failed to prime the neuroinflammatory response to tumors.