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

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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.

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Acknowledgements

The authors would like to thank Dr. Eduardo Vázquez-Garza for their excellent technical assistance in flow cytometry and Lucia Villareal for their help with anthropometry measurements.

Funding

This work was partially supported by Cardiovascular Medicine Research Group- Tecnologico de Monterrey 0020CAT131 as well as CONACYT-México grants 151136 and 256577 (G. G-Rivas) and by the XIGNUX foundation 00220CIE241 (LE-M). JR V-C was supported by the Graduate Student Fellowship of CONACYT. This work was submitted in partial fulfillment of the requirements for the Master’s degree (JR V-C) for the Master in Biomedical Sciences at Tecnologico de Monterrey.

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Correspondence to L. Elizondo-Montemayor or G. García-Rivas.

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Jose Romeo Villarreal-Calderón, Elena Cristina Castillo, Ricardo X. Cuellar-Tamez, Manuel García-Garza, Leticia Elizondo-Montemayor, and Gerardo García-Rivas declare that they have no conflicts of interest or financial ties to disclose.

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Villarreal-Calderón, J.R., Castillo, E.C., Cuellar-Tamez, R.X. et al. Reduced Th1 response is associated with lower glycolytic activity in activated peripheral blood mononuclear cells after metabolic and bariatric surgery. J Endocrinol Invest 44, 2819–2830 (2021). https://doi.org/10.1007/s40618-021-01587-4

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