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

Maria Dulfary Sanchez-Pino; William S Richardson; Jovanny Zabaleta; Ramesh Thylur Puttalingaiah; Andrew G Chapple; Jiao Liu; Yonghyan Kim; Michelle Ponder; Randi DeArmitt; Lyndsey Buckner Baiamonte; Dorota Wyczechowska; Liqin Zheng; Amir A Al-Khami; Jone Garai; Rachel Martini; Melissa Davis; Jessica Koller Gorham; James B Wooldridge; Paulo C Rodriguez; Lucio Miele; Augusto C Ochoa

doi:10.1016/j.ebiom.2022.103910

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

EBioMedicine. 2022 Mar:77:103910. doi: 10.1016/j.ebiom.2022.103910. Epub 2022 Mar 3.

Authors

Maria Dulfary Sanchez-Pino¹, William S Richardson², Jovanny Zabaleta³, Ramesh Thylur Puttalingaiah³, Andrew G Chapple⁴, Jiao Liu³, Yonghyan Kim³, Michelle Ponder⁵, Randi DeArmitt⁵, Lyndsey Buckner Baiamonte⁵, Dorota Wyczechowska³, Liqin Zheng³, Amir A Al-Khami³, Jone Garai³, Rachel Martini⁶, Melissa Davis⁶, Jessica Koller Gorham², James B Wooldridge², Paulo C Rodriguez⁷, Lucio Miele⁸, Augusto C Ochoa⁹

Affiliations

¹ Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, LSU-LCMC Cancer Center, Louisiana State University Health Sciences Center, 1700 Tulane Ave, Room 911, New Orleans, LA 70112, USA; Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA. Electronic address: msanc2@lsuhsc.edu.
² Department of Surgery, Ochsner Clinic Foundation, New Orleans, LA, USA.
³ Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, LSU-LCMC Cancer Center, Louisiana State University Health Sciences Center, 1700 Tulane Ave, Room 911, New Orleans, LA 70112, USA.
⁴ Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
⁵ Biorepository Unit, Ochsner Medical Center, New Orleans, LA, USA.
⁶ Department of Surgery and Surgical Oncology, Cell and Developmental Biology in Surgery, Weill Cornell Medicine, New York, NY, USA.
⁷ Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
⁸ Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
⁹ Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, LSU-LCMC Cancer Center, Louisiana State University Health Sciences Center, 1700 Tulane Ave, Room 911, New Orleans, LA 70112, USA; Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: 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).

Keywords: Bariatric surgery; Inflammation; LDN; Low-density neutrophils; Obesity.

Published by Elsevier B.V.

MeSH terms

Bariatric Surgery* / methods
Case-Control Studies
Humans
Longitudinal Studies
Neutrophils / metabolism
Obesity, Morbid* / complications
Obesity, Morbid* / metabolism
Obesity, Morbid* / surgery
Prospective Studies

Abstract

MeSH terms

Grants and funding