Abstract
Objective Tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) is attracting attention for its role in the physiopathology of metabolic disease/diabetes. Evidence suggests that it might protect against metabolic abnormalities driven by obesity-induced dysregulated secretion of adipokines, but this role of TRAIL has not yet been fully established. On this basis, we aimed to investigate the potential association between TRAIL and adipokine levels in a cohort of subjects in which age/gender/hormonal interferences were excluded. Methods Serum levels of TRAIL and a panel of adipokines were measured in postmenopausal women (n = 147) stratified according to waist circumference measures as normal, overweight, or obese. The panel of adipokines included interleukin- (IL-) 6, IL-8, IL-1β, adipsin, lipocalin-2/neutrophil gelatinase-associated lipocalin (ngal), TNF-alpha, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, hepatocyte growth factor, resistin, leptin, adiponectin, and nerve growth factor. Results Low serum TRAIL concentration (deciles I–IV) was significantly and inversely correlated with resistin and lipocalin 2/ngal levels (r = −0.502 and p < 0.001 and r = −0.360 and p < 0.01, resp.). Both associations retained their statistical significance after adjustment for confounding factors, such as waist circumference and age. Conclusions Our data indicate a link between low circulating levels of TRAIL and markers of obesity-induced diseases (resistin and lipocalin-2/ngal), highlighting a new potential axis of TRAIL functions.
Highlights
Tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily expressed by various cell types, mostly in the immune system [1]
In order to investigate the relationship between the serum levels of TRAIL and adipokines, waist circumference was evaluated for correlation studies, and the cohort was stratified according to abdominal obesity (WHO classification) in normal weight, overweight (80–87.9 cm), and obese (≥88 cm) groups, which were represented (Table 1)
The role of TRAIL in weight gain-associated metabolic alterations and obesity has not been fully established, the general view is that the cytokine might mediate adaptive biological responses to the obesity-induced perturbation of metabolism and immune homeostasis [2]
Summary
Tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily expressed by various cell types, mostly in the immune system [1]. There have been many studies focused on the role of TRAIL in cancer because one of the best-characterized properties of this molecule is its ability to induce apoptosis in tumors and immortalized cells [1]. The action of TRAIL is not exclusively exerted on transformed cells, and it may be effective in primary cells, including immune cells [2, 3]. Recent findings have highlighted a potential role of this molecule in a number of diseases other than cancer, such as diabetes, atherosclerosis, and hypertension [5, 6]
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