High levels of LIGHT/TNFSF14 in patients with Prader–Willi syndrome

Abstract

Purpose/methods Prader–Willi syndrome (PWS) is a rare genetic disorder displaying different clinical features, including obesity and bone impairment. LIGHT/TNFSF14 is a cytokine produced by immune cells affecting both fat and bone metabolism. The present study aimed to evaluate LIGHT serum levels in 28 children and 52 adult PWS patients compared to age and sex-matched controls, as well as correlations with parameters of bone and fat metabolism. Results Median serum LIGHT levels were significantly increased in pediatric PWS with respect to controls [255.82 (284.43) pg/ml vs 168.11 (76.23) pg/ml, p ≤ 0.02] as well as in adult PWS compared to controls [296.85 (895.95) pg/ml vs 134.18 (141.18) pg/ml, p ≤ 0.001]. In pediatric PWS, LIGHT levels were positively correlated with weight-SDS, height-SDS, and glucose levels, and negatively with total 25 (OH) vitamin D, cholesterol, LDL cholesterol and triglycerides. Additionally, LIGHT levels were negatively correlated with total BMD and fat mass. In adult PWS, LIGHT levels were positively correlated with weight, HDL cholesterol and PTH, and negatively with glucose, insulin, HOMA-IR, total cholesterol, LDL cholesterol, triglycerides, calcium, phosphorus, 25(OH)Vitamin D as well as with instrumental parameters of bone and fat quality. Consistently, multiple regression analysis showed that LIGHT serum levels in pediatric and adult PWS were predicted by different parameters including 25 (OH) Vitamin D as well as DXA parameters of bone and fat quality. Conclusions In PWS children and adults the high levels of LIGHT could represent a marker of the altered bone and fat metabolism.

LIGHT/TNFSF14 Affects Adipose Tissue Phenotype

“…The interest in exploring the role of LIGHT in HFD arises from the high levels of this cytokine detected in obesity, together with the conflicting results on the role of LIGHT in adipogenesis. The increased circulating levels of LIGHT have been demonstrated in obese pediatric and adult subjects, but also in genetic obesity associated with Prader-Willy patients [6][7][8]. Consistently, different murine models were used to study the role of LIGHT in obesity [13][14][15][16][17][18]24], and the complexity is also associated with the heterogeneous microenvironment that characterizes fat tissue.…”

“…However, with the primary objective of extending the use of this immunotherapy to other diseases, different studies have explored the role of LIGHT in metabolic diseases, including obesity. Previously published papers have reported an increase in circulating LIGHT levels in obese adults as well as in children [5,6], Prader Willi syndrome subjects displaying genetic obesity [7,8], and mice subjected to High Fat Diet (HFD composition: 19 MJ kg −1 , 35% of energy from carbohydrate, 42% from fat, 23% from protein) [9]. Conversely, an anti-inflammatory diet reduced systemic inflammation and thus LIGHT levels [10].…”

LIGHT protein: A novel gingival crevicular fluid biomarker associated with increased probing depth after periodontal surgery

“…In obese individuals, serum levels of LIGHT correlate with reduced bone mineral density (Faienza et al, 2023). In cultures of peripheral blood mononuclear cells isolated from obese subjects, anti-LIGHT antibodies inhibit osteoclastogenesis .…”

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

“…LIGHT/TNFSF14 is a cytokine produced by immune cells that affects both fat and bone metabolism; Faienza et al showed that serum LIGHT levels were significantly higher in both PWS children and PWS adults than in controls (96). Additionally, LIGHT levels were found to have a negative correlation with DEXA parameters.…”