Uncovering the impact of weight loss on obesity-induced changes in B cell metabolism and function

Obesity is still increasing in prevalence globally and is an important risk factor for poor health and mortality. Chronic low-grade inflammation in obese individuals is closely associated with the development of comorbidities, including type 2 diabetes mellitus, cardiovascular disease and cancer. B-cells contribute to this low-level inflammation in obesity. This has been suggested to occur through enhanced pathogenic antibody and cytokine secretion as well as through antigen presentation to augment proinflammatory T-cell function. Indeed, obese individuals have altered peripheral B-cell composition, including an increase in exhausted memory B-cells and a decrease in regulatory B-cells. As further evidence of dysregulated B-cell compartment, reduced antibody responses to influenza vaccination have been reported in obesity. Using a combination of flow-cytometry, tissue culture and metabolic profiling, and building on our existing expertise in investigating B-cells in immune-related pathology as well as clinical nutrition and obesity, we will: (1) establish whether peripheral blood B-cell defects can be corrected by weight reduction in obese individuals; (2) delineate the metabolic programs in B-cells in obese and lean individuals and how these are affected by weight loss in obesity; (3) investigate the relationship between B-cell dysregulation in peripheral blood and adipose tissue in obese individuals.