Splenectomy fails to attenuate immuno-hematologic changes after rodent vertical sleeve gastrectomy

Abstract

Bariatric surgery is on the rise for long-term weight loss and produces various positive metabolic health benefits. The mechanisms that produce surgical weight loss are not yet fully understood. Previous studies showed vertical sleeve gastrectomy prior to gestation resulted in reduced peripheral blood lymphocytes measured during pregnancy due to an undetermined etiology. Further, elevated splenic weight has been associated with vertical sleeve gastrectomy surgery. We hypothesized that perhaps altered splenic filtration was trapping circulating lymphocytes and thus reducing peripheral blood lymphocytes in circulation and contributing to increased spleen weight. We posited whether removal of the spleen concomitant with the stomach surgery may result in an improved immune phenotype. We evaluated female long Evans rats having received Sham surgery or vertical sleeve gastrectomy, with or without splenectomy to determine the contribution of the spleen on metabolic and immune factors after vertical sleeve gastrectomy. Vertical sleeve gastrectomy animals lost significant amounts of body mass and fat mass and ate less in comparison to Sham females during the first five post-operative weeks, but there was no specific effect of the loss of spleen on body mass, fat mass, or food intake. During the post-operative week 6, animals were euthanized and blood recovered for cell sorting of immune cells. There was a reduction in CD3+ total T cells, CD3/CD4+ helper T cells, and CD3/CD8+ cytotoxic T cells, main effect of both bariatric surgery (P < 0.0001) and splenectomy (P < 0.01). Furthermore, there was a significant increase in CD45RA+ B cells as a result of splenectomy (P < 0.001), but a significant reduction in B cells as a result of VSG surgery (P < 0.05). The changes in total T cells but not B cells were strongly correlated with fat mass. Further studies are needed to understand the cause of the immune changes after surgical weight loss.

Impact statement

Bariatric surgery and in particular vertical sleeve gastrectomy are the fastest growing means for robust amelioration of the comorbidities of obesity. The ramifications of the surgeries on immune health are of important consequence because of the connectivity of immunity with every organ system. The current work reports on the impact of the surgery on the spleen, thymus, and peripheral blood in a rodent model that mimics human surgical outcomes. We demonstrate altered immune health in the VSG rat.