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. 2015 Jan;39(1):26-32.
doi: 10.1038/ijo.2014.194. Epub 2014 Nov 12.

Obesity is associated with more activated neutrophils in African American male youth

X Xu  1 , S Su  1 , X Wang  1 , V Barnes  1 , C De Miguel  2 , D Ownby  3 , J Pollock  2 , H Snieder  4 , W Chen  5 , X Wang  1
Affiliations

Obesity is associated with more activated neutrophils in African American male youth

X Xu et al. Int J Obes (Lond). 2015 Jan.

Abstract

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 (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).

Conclusion: 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.

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Figures

Figure 1
Figure 1. Volcano plot of obesity related differentially expressed genes in males and females
(A) Volcano plot of the log2 fold change of gene expression levels (X-axis) against the –log10 P-value (Y-axis) comparing obese and lean males. (B) Volcano plot of the log2 fold change of gene expression levels (X-axis) against the –log10 P-value (Y-axis) comparing obese and lean females.
Figure 2
Figure 2. Real time PCR replication of ELANE and MPO in neutrophils
(A) Histogram showing the gene expression levels of ELANE relative to β-actin (Y-axis, %) comparing obese and lean males (p=0.01 with age adjusted) and females (p=0.09 with age adjusted), respectively (B) Histogram showing the gene expression levels of MPO relative to β-actin (Y-axis, %) comparing obese and lean males (p=0.02 with age adjusted) and females (p=0.20 with age adjusted), respectively
See this image and copyright information in PMC

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