Increased inflammatory low-density neutrophils in severe obesity and effect of bariatric surgery: Results from case-control and prospective cohort studies.

Abstract

Low-density neutrophils (LDN) are increased in several inflammatory diseases and may also play a role in the low-grade chronic inflammation associated with obesity. Here we explored their role in obesity, determined their gene signatures, and assessed the effect of bariatric surgery. We compared the number, function, and gene expression profiles of circulating LDN in morbidly obese patients (MOP, n=27; body mass index (BMI) > 40 Kg/m²) and normal-weight controls (NWC, n=20; BMI < 25 Kg/m²) in a case-control study. Additionally, in a prospective longitudinal study, we measured changes in the frequency of LDN after bariatric surgery (n=36) and tested for associations with metabolic and inflammatory parameters. LDN and inflammatory markers were significantly increased in MOP compared to NWC. Transcriptome analysis showed increased neutrophil-related gene expression signatures associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of reactive oxygen species (ROS). Circulating LDN in MOP significantly decreased after bariatric surgery in parallel with BMI, metabolic syndrome, and inflammatory markers. Obesity increases LDN displaying an inflammatory gene signature. Our results suggest that LDN may represent a neutrophil subset associated with chronic inflammation, a feature of obesity that has been previously associated with the appearance and progression of co-morbidities. Furthermore, bariatric surgery, as an efficient therapy for severe obesity, reduces LDN in circulation and improves several components of the metabolic syndrome supporting its recognized anti-inflammatory and beneficial metabolic effects. This work was supported in part by grants from the National Institutes of Health (NIH; 5P30GM114732-02, P20CA233374 - A. Ochoa and L. Miele), Pennington Biomedical NORC (P30DK072476 - E. Ravussin & LSU-NO Stanley S. Scott Cancer Center and Louisiana Clinical and Translational Science Center (LACaTS; U54-GM104940 - J. Kirwan).