Obesity is associated with more activated neutrophils in African American male youth.
BACKGROUND
There is emerging evidence suggesting the role of peripheral blood leukocytes in the pathogenesis of obesity and related diseases. However, few studies have taken a genome-wide approach to investigating gene expression profiles in peripheral leukocytes between obese and lean individuals with the consideration of obesity-related shifts in leukocyte types.


METHODS
We conducted this study in 95 African Americans (AAs) of both genders (age 14-20 years, 46 lean and 49 obese). Complete blood count with differential test (CBC) was performed in whole blood. Genome-wide gene expression analysis was obtained using the Illumina HumanHT-12 V4 Beadchip with RNA extracted from peripheral leukocytes. Out of the 95 participants, 64 had neutrophils stored. The validation study was based on real-time PCR with RNA extracted from purified neutrophils.


RESULTS
CBC test suggested that, in males, obesity was associated with increased neutrophil percentage (P=0.03). Genome-wide gene expression analysis showed that, in males, the majority of the most differentially expressed genes were related to neutrophil activation. Validation of the gene expression levels of ELANE (neutrophil elastase) and MPO (myeloperoxidase) in purified neutrophils demonstrated that the expression of these two genes--important biomarkers of neutrophils activation--were significantly elevated in obese males (P=0.01 and P=0.02, respectively).


CONCLUSIONS
The identification of increased neutrophil percentage and activation in obese AA males suggests that neutrophils have an essential role in the pathogenesis of obesity-related disease. Further functional and mechanistic studies on neutrophils may contribute to the development of novel intervention strategies reducing the burden associated with obesity-related health problems.
Department of Pediatrics, Georgia Prevention Center, Institute of Public and Preventive Health, Georgia Regents University, Augusta, GA, USA.
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0000000297801570
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Xu
Department of Pediatrics, Georgia Prevention Center, Institute of Public and Preventive Health, Georgia Regents University, Augusta, GA, USA.
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Su
Department of Pediatrics, Georgia Prevention Center, Institute of Public and Preventive Health, Georgia Regents University, Augusta, GA, USA.
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Wang
Department of Pediatrics, Georgia Prevention Center, Institute of Public and Preventive Health, Georgia Regents University, Augusta, GA, USA.
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Barnes
Cardio-Rental Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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De Miguel
Department of Experimental Medicine, Georgia Regents University, Augusta, GA, USA.
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Ownby
Cardio-Rental Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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Pollock
Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands.
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Snieder
Department of Physiology and Endocrinology, Georgia Regents University, Augusta, GA, USA.
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Chen
Department of Pediatrics, Georgia Prevention Center, Institute of Public and Preventive Health, Georgia Regents University, Augusta, GA, USA.
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Wang
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D008297:Male; D018375:Neutrophil Activation / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D014481:United States / Q000453:epidemiology