Background: Obesity during childhood has been demonstrated to exert profound and lasting effects on bone strength and fracture risk. Furthermore, obesity is characterized by chronic inflammation and oxidative stress, with an increase in the mediators of innate immunity. It has been found that skeletal homeostasis is influenced by immune cells. LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells) is emerging among cytokines produced by immune cells, also involved in inflammation and bone disease. It is a member of the tumor necrosis factor (TNF) family, primarily expressed on immune cells, which has a role in adipogenesis and osteoclastogenesis.
Objective and hypotheses: We aimed to analyze whether LIGHT has a role in the bone fragility associated to childhood obesity.
Method: LIGHT levels has been measured in the sera from 10 obese children (aged 10-8±2.56 yrs) and 10 sex and age matched controls. Its expression has been evaluated by flow cytometry in circulating cells from patients and controls. PBMCs were cultured in presence/absence of neutralizing anti-LIGHT antibody. Mature multinucleated osteoclasts (OCs) were identified as TRAP+ cells. Bone status was assessed by QUS through BTT-Z-score and Ad-Sos-Z-score evaluation.
Results: Higher serum levels of LIGHT were measured in obese children compared to controls (520±265 ng/ml vs 240±156, P<0.01 ng/ml). In the same patients, elevated expression of LIGHT on monocytes was found. In culture spontaneously OC formation occurred, without the addition of exogenous growth factors. Interestingly, this spontaneous OC formation is inhibited in vitro by anti-LIGHT neutralizing antibody. Additionally, obese children had significantly reduced QUS parameters compared to the controls (P<0.01). Interestingly, we found that BTT-Z-score inversely correlated with LIGHT serum levels (r=−0.750; P=0.03).
Conclusion: LIGHT could represent a key molecule linking inflammation-fat-bone in obese children.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology