Metabolic fingerprint of insulin resistance in human polymorphonuclear leucocytes

Abstract

The present study was aimed at determining the metabolic profile of PMNs in obese subjects, and to explore its potential relationship with insulin resistance (IR). To achieve this goal, a pilot clinical study was performed using PMNs from 17 patients with obesity and IR, and 17 lean controls without IR, which was validated in an additional smaller cohort (consisting of 10 patients and 10 controls). PMNs were isolated from peripheral blood and nuclear magnetic resonance was used to perform the metabolomic analysis. A total of 48 metabolites were quantified. The main metabolic change found in PMNs was a significant increase in 2-aminoisobutyric acid with a direct correlation with HOMA-IR (p<0.001), BMI (p<0.000001) and waist circumference (p<0.000001). By contrast, a decrease of 3-hydroxyisovalerate was observed with an inverse correlation with HOMA-IR (p = 0.001), BMI (p = 0.001) and waist circumference (p = 0.0001). Notably, the metabolic profile in plasma was different than that obtained in PMNs. In summary, our results suggest that the change in 3-hydroxyisovalerate and 2-aminoisobutyric is the key metabolic fingerprint in PMNs of obese subjects with IR. In addition, our methodology could be an easy and reliable tool for monitoring the effect of treatments in the setting of precision medicine.

A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes

“…A representative spectrum of RBC extracts is shown in Figure 1 , where several metabolites could be identified and quantified, based on previous data [ 56 , 57 ] and 2D-NMR spectra ( Supplementary Table S1 ).…”

Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers

“…In this context, metabolomics approaches have shown great potential for the identification on new clinically relevant potential biomarkers. Metabolic signatures have proven their value in several diseases, such as cancer [14][15][16][17], gynaecological diseases [18], hypertension [19] and insulin resistance [20]. In contrast, fewer studies have specifically addressed the metabolomic alterations that occur in infectious diseases [21][22][23].…”

Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway

“…It has been shown that microcirculatory dysfunction and immune adjustment are associated with the pathogenesis of liver IR damage (26,27). Previous studies have reported that neutrophil inflammatory cells were detected following IR injury in the liver (28)(29)(30). In conditions such as ischemia, hypoxia and IR liver injury, a large number of oxygen free radicals can be produced, which induce the oxidative stress response and liver damage (31).…”