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. METHOD: We conducted this study in 95 African Americans of both genders (age 14-20, 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 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 polymerase chain reaction 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). CONCLUSION: The identification of increased neutrophil percentage and activation in obese African American males suggests that neutrophils play 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.