Reduced Th1 response is associated with lower glycolytic activity in activated peripheral blood mononuclear cells after metabolic and bariatric surgery

Abstract

Background: Obesity promotes cellular immunometabolism changes that trigger the activation of macrophages and lymphocytes, leading to systemic inflammation. Activated leukocytes undergo metabolic reprogramming, increasing glycolytic activity.

Objective: To examine whether the reduction in the inflammatory state associated with bariatric surgery is associated with decreased glycolytic activity in leukocytes. Setting Single-center, prospective observational study.

Methods: This study involved 18 patients with obesity undergoing bariatric surgery. All measurements were performed preoperatively and six months postoperatively. Peripheral blood mononuclear cells and plasma were obtained to determine the glycolytic rate and mitochondrial membrane potential as surrogates of the metabolic switching and high-sensitivity C-reactive protein, adipokines, and CD69 expression as inflammatory and activation markers.

Results: Glycolytic activity engaged by CD3/CD28 activation was reduced six months after bariatric surgery, associated with decreased levels of T helper (Th) 1 and Th17 signature cytokines. An overall reduction in inflammatory markers was observed, which correlated with a higher adiponectin/leptin ratio.

Conclusions: Metabolic and bariatric surgery-induced weight loss leads to reprogramming in T cells' metabolic machinery, resulting in reduced stimulation of glycolysis after activation, which may explain the decrease in systemic inflammation mediated by cytokines such as interferon-γ and interleukin-17A.

Keywords: Activation; Bariatric surgery; Immunemetabolism; Inflammation; Metabolic reprogramming; PBMCs.