Shedding “LIGHT” on the Link between Bone and Fat in Obese Children and Adolescents

Brunetti, Giacomina; Faienza, Maria Felicia; Piacente, Laura; Storlino, Giuseppina; Oranger, Angela; Damato, G.; Filippo, Gianpaolo De; Colucci, Silvia; Grano, Maria

doi:10.3390/ijms21134739

Cited by 6 publications

(8 citation statements)

References 60 publications

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“…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.…”

Section: Discussionmentioning

confidence: 97%

“…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].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the authors suggested that LIGHT, as a cytokine produced by activated immune cells, supports immune cell activation at the expense of adiposity. Murine models of obesity using LIGHT deficient mice have not provided clear results [7,15,17]. In particular, in a model of HFD, Tnfrsf14 −/− mice developed increased obesity, glucose intolerance, and hepatosteatosis [9].…”

Section: Introductionmentioning

confidence: 99%

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LIGHT/TNFSF14 Affects Adipose Tissue Phenotype

Oranger,

Colaianni,

Ingravallo

et al. 2024

IJMS

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LIGHT/TNFSF14 is linked to several signaling pathways as a crucial member of a larger immunoregulatory network. It is primarily expressed in inflammatory effector cells, and high levels of LIGHT have been reported in obesity. Thus, with the aim of deepening the knowledge of the role of LIGHT on adipose tissue phenotype, we studied wild-type (WT), Tnfsf14−/−, Rag−/− and Rag-/Tnfsf14- (DKO) mice fed a normal diet (ND) or high-fat diet (HFD). Our results show that, although there is no significant weight gain between the mice with different genotypes, it is significant within each of them. We also detected an increase in visceral White Adipose Tissue (vWAT) weight in all mice fed HFD, together with the lowest levels of vWAT weight in Tnfsf14−/− and DKO mice fed ND with respect to the other strain. Inguinal WAT (iWAT) weight is significantly affected by genotype and HFD. The least amount of iWAT was detected in DKO mice fed ND. Histological analysis of vWAT showed that both the genotype and the diet significantly affect the adipocyte area, whereas the number is affected only by the genotype. In iWAT, the genotype and the diet significantly affect mean adipocyte area and number; interestingly, the area with the least adipocyte was detected in DKO mice fed ND, suggesting a potential browning effect due to the simultaneous lack of mature lymphocytes and LIGHT. Consistently, Uncoupling Protein 1 (UCP1) staining of iWAT demonstrated that few positive brown adipocytes appeared in DKO mice. Furthermore, LIGHT deficiency is associated with greater levels of UCP1, highlighting the lack of its expression in Rag−/− mice. Liver examination showed that all mice fed HFD had a steatotic liver, but it was particularly evident for DKO mice. In conclusion, our study demonstrates that the adipose tissue phenotype is affected by LIGHT levels but also much more by mature lymphocytes.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LIGHT/TNFSF14 Affects Adipose Tissue Phenotype

Oranger,

Colaianni,

Ingravallo

et al. 2024

IJMS

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“…A reduced bone mass has been demonstrated in Tnfsf14 deficient mice [ 15 ], whereas high levels of this cytokine have been found in obese subjects [ 16 , 17 ] and in some bone diseases [ 18 – 20 ]. However, the role of LIGHT in adipogenesis is still debated.…”

Section: Introductionmentioning

confidence: 99%

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

Faienza

Brunetti

Fintini

et al. 2023

J Endocrinol Invest

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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.

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“…It is known that obese children have low bone mineral density and a greater risk of osteoporosis and fractures [ 24 ]. In the attempt to analyze the pathogenesis of this disease, Brunetti et al demonstrated high levels of LIGHT in sera and on circulating cells of obese children and adolescents respect the controls [ 25 ]. The same authors also reported that in cultures of peripheral blood mononuclear cells from obese subjects, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition.…”

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confidence: 99%