Abstract
Obesity may affect bone health, but literature reports are contradictory about the correlation of body mass index (BMI) and bone markers. LIGHT, one of the immunostimulatory cytokines regulating the homeostasis of bone and adipose tissue, could be involved in obesity. The study involved 111 obese subjects (12.21 ± 3.71 years) and 45 controls. Patients underwent the evaluation of bone status by quantitative ultrasonography (QUS). LIGHT amounts were evaluated in sera by ELISA, whereas its expression on peripheral blood cells was evaluated by flow cytometry. Osteoclastogenesis was performed by culturing peripheral blood mononuclear cells (PBMCs) with or without anti-LIGHT antibodies. Obese patients showed significant high BMI-standard deviation score (SDS), weight-SDS, and Homeostatic model assessment for insulin resistance (HOMA-IR) that negatively correlated with the reduced Amplitude Dependent Speed of Sound (AD-SoS)-Z-score and Bone Transmission Time (BTT-Z)-score. They displayed significantly higher serum levels of LIGHT compared with controls (497.30 ± 363.45 pg/mL vs. 186.06 ± 101.41 pg/mL, p < 0.001). LIGHT expression on monocytes, CD3+-T-cells, and neutrophils was also higher in obese patients than in the controls. Finally, in PBMC cultures, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition. Our study highlighted the high serum levels of LIGHT in obese children and adolescents, and its relationship with both the grade of obesity and bone impairment.
Highlights
There are numerous evidences showing that disorders with altered bone development, during growth, may affect bone health in adulthood [1]
Obese children, whose numbers increase in almost all countries, have a fivefold increased risk to remain obese during adulthood and to develop non-communicable diseases (NCDs) at a younger age, like cardiovascular diseases [6,7], different types of cancer, and metabolic and musculoskeletal disorders [8,9,10,11,12]
We demonstrated that the increasing doses of anti-LIGHT antibodies induced a dose-dependent reduction of osteoclast number in peripheral blood mononuclear cells (PBMCs)
Summary
There are numerous evidences showing that disorders with altered bone development, during growth, may affect bone health in adulthood [1]. Many pro-inflammatory cytokines involved in obesity are crucial mediators of osteoclastogenesis, with consequent increase of bone resorption activity [18], and supporting the link between obesity and altered bone turnover. One of these cytokines could be represented by LIGHT (homologous to Lymphotoxins exhibiting Inducible expression and competing with herpes simplex virus Glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) [19,20,21,22,23,24,25,26]. Based on literature data, this study was designed to evaluate the serum levels of LIGHT and its correlation with bone metabolism markers and quantitative ultrasound measurements of bone quality in a group of children and adolescents with different grades of obesity
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