Plasma and Adipose Tissue Levels of Selected Growth/Inhibitory Factors, Proteolytic Enzymes and Sphingosine-1-Phosphate in Humans

Abstract

Recent studies have shown that adipose tissue (AT), while implicated in orchestrating the sophisticated process termed “immunometabolism,” may also serve as a potential niche for various bone marrow-derived (stem) cells. However, at present, the direct biochemical and immunomodulatory composition of the human AT environment has not been studied. Several substances that might play a crucial role in regulating stem cell migration and/or homing to AT, have been implicated, namely, hepatocyte/vascular endothelial growth factor (VEGF/HGF), leukemia inhibitory factor (LIF), and sphingosine-1-phosphate (SIP). Therefore, we examined and compared the AT concentrations of these substances between plasma, subcutaneous, and omental AT samples derived from 35 generally healthy subjects. VEGF, HGF, LIF, and metalloproteinases (MMP)-2 and MMP9 levels were measured using ELISA, and S1P concentrations were analyzed using reverse-phase high performance liquid chromatography. We found that AT levels of analyzed growth/inhibitory factors were generally comparable (VEGF and LIF) or even higher (HGF) than the corresponding levels in the peripheral blood, particularly in overweight/obese subjects. In subcutaneous AT, significantly lower VEGF and LIF concentrations were observed, and these were accompanied by higher MMP levels. No depot-specific differences in S1P concentrations were found in all examined groups. Moreover, we established several associations between analyzed molecular substances and body composition, BMI, or adiposity index of the examined patients. In conclusion, our study revealed that human AT possesses relatively high levels of selected growth/inhibitory factors and of chemoattractants involved in the regulation of stem cell trafficking, and these factors are associated with the metabolic status of an individual. Further studies are needed to clearly establish the role of these factors in the regulation of bone marrow-derived (stem) cell homeostasis and homing in human AT.