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
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).
