Mechanisms and Treatments of Obesity-related Inflammation

Chronic inflammation contributes to the pathophysiology of obesity-related diseases, making it essential to identify strategies that reduce inflammation and restore immune balance. In Part 1, we investigated how obesity-related cytokines regulate B7H3 and its immunosuppressive effects in TNBC. We found that IFN-γ and TNF, individually and together, induce B7H3 expression in TNBC. Moreover, B7H3 promotes an immunosuppressive tumor microenvironment in an obesity-dependent manner, suggesting that metabolic factors shape tumor immunity and may drive cancer progression. In Part 2, we examined whether GLP-1RA can modulate immune cell metabolism and function to counter obesity-induced inflammation. GLP-1RA directly alters T cell metabolism and function in a subset- and obesity-dependent manner. In lean T cells, it reduces fatty acid uptake and mitochondrial activity, leading to decreased pro-inflammatory cytokine production. These effects are attenuated in obese T cells, indicating impaired metabolic responsiveness. Together, these findings support a direct immunometabolic role for GLP-1RA in reducing inflammation.