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

EBioMedicine (Mar 2022)

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

Affiliations

Maria Dulfary Sanchez-Pino: 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; Corresponding author at: 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.
William S. Richardson: Department of Surgery, Ochsner Clinic Foundation, New Orleans, LA, USA
Jovanny Zabaleta: 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
Ramesh Thylur Puttalingaiah: 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
Andrew G. Chapple: Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA
Jiao Liu: 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
Yonghyan Kim: 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
Michelle Ponder: Biorepository Unit, Ochsner Medical Center, New Orleans, LA, USA
Randi DeArmitt: Biorepository Unit, Ochsner Medical Center, New Orleans, LA, USA
Lyndsey Buckner Baiamonte: Biorepository Unit, Ochsner Medical Center, New Orleans, LA, USA
Dorota Wyczechowska: 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
Liqin Zheng: 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
Amir A. Al-Khami: 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
Jone Garai: 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
Rachel Martini: Department of Surgery and Surgical Oncology, Cell and Developmental Biology in Surgery, Weill Cornell Medicine, New York, NY, USA
Melissa Davis: Department of Surgery and Surgical Oncology, Cell and Developmental Biology in Surgery, Weill Cornell Medicine, New York, NY, USA
Jessica Koller Gorham: Department of Surgery, Ochsner Clinic Foundation, New Orleans, LA, USA
James B. Wooldridge: Department of Surgery, Ochsner Clinic Foundation, New Orleans, LA, USA
Paulo C. Rodriguez: Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
Lucio Miele: Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
Augusto C. Ochoa: 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

Journal volume & issue: Vol. 77
p. 103910

Abstract

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Summary: 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).

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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