ALPL, A Novel Marker Of Neutrophil Activation In Response To Obesity

Abstract

Low‐grade systemic inflammation accompanies obesity and etiologically contributes to obesity‐induced cardiovascular disease (CVD). Neutrophils represent the most abundant type of leukocytes in humans and neutrophil activation is a fundamental process in the inflammatory response. Growing evidence supports that neutrophil is most likely to be the target peripheral leukocyte subtype initiating the inflammatory cascade in response to obesity. However, few studies have systematically assessed the molecular changes of neutrophils in response to obesity. In this study, a hypothesis‐free OMIC approach (i.e. the discovery phase) and a target approach (i.e. the validation phase) were used to identify obesity related neutrophil activation markers and their roles on CVD risks. In the discovery phase, genome wide DNA methylation, RNA‐sequencing and quantitative proteomics were obtained from the purified neutrophils of 12 obese cases and 12 lean controls. Significant difference was found for one gene, alkaline phosphatase, liver/bone/kidney (ALPL), across 3 OMIC platforms. In the validation phase, the expression levels of ALPL in leukocytes were obtained from 81 obese cases and 83 lean controls. The ALPL expression levels were significantly higher in obese compared with lean subjects (p=0.021). Within obese population, we observed that ALPL expression level showed significantly positive association with CVD risk factors including systolic blood pressure (BP) (p=0.032), diastolic BP (p=0.011) and mean arterial pressure (p=0.008), as well as borderline significance with fasting insulin (p=0.059). This study identified one novel marker of neutrophil activation in response to obesity and provided further evidence that obesity induced change in ALPL expression is associated with CVD risk factors.Support or Funding InformationNHLBI HL105689This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.