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  • Original Article
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LIGHT (TNFSF14) inhibits adipose differentiation without affecting adipocyte metabolism

International Journal of Obesity volume 35, pages 208–216 (2011)Cite this article

Subjects

Abstract

Objective:

The member of the tumor necrosis factor family LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells; TNFSF14 (tumor necrosis factor super family protein 14) is primarily expressed in lymphocytes, in which it induces the expression of pro-inflammatory cytokines and alterations of lipid homeostasis. Recently, the protein was shown to be upregulated in obesity and to induce cytokine secretion from adipocytes.

Research Methods and Procedures:

Using an automated complementary DNA (cDNA) screen, LIGHT was identified to inhibit adipose differentiation. As cellular models for adipogenesis mouse 3T3-L1, human SGBS (Simpson-Golabi-Behmel syndrome) and primary human preadipocytes differentiated in vitro were used as well as primary human adipocytes to study adipocyte functions. Analysis of lipid deposition by Oil Red O staining, mRNA expression by quantitative reverse transcriptase-PCR, nuclear factor (NF)-κB activation as well as protein secretion by enzyme linked immunosorbent assay and Luminex technology was performed.

Results:

LIGHT was found to inhibit lipid accumulation in the three models of preadipocytes in a dose-dependent manner without cytotoxic effects. This inhibition of differentiation was probably because of interference at early steps of adipogenesis, as early exposure during differentiation showed the strongest effect, as assessed by decreased peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα) mRNA expression. In contrast to TNFα, basal and insulin-stimulated glucose uptake and lipolysis of terminally differentiated mature adipocytes were not altered in the presence of LIGHT. At a concentration sufficient to inhibit differentiation, secretion of proinflammatory cytokines was not significantly induced and NF-κB activity was only modestly induced compared with TNFα.

Conclusion:

LIGHT is a novel inhibitor of human adipocyte differentiation without adversely influencing central metabolic pathways in adipocytes.

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Acknowledgements

We thank Drs Hoffmann and von Finckenstein and their teams for support in obtaining adipose tissue samples. We are grateful to Dr Kerstin Schnäbele from the Department of Biofunctionality of Foods for access to flow cytometry. We thank Silke Ecklebe and Lydia Gehrke for their excellent technical assistance. PFP is funded by a Margarete von Wrangell scholarship financed by the Baden-Wuerttemberg Ministry of Science, Research and Arts and the European Social Fund. Parts of the project are financed by the German Research Foundation (WA 1096/3-3 to MW).

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Author notes

  1. A Finck & U Brinkmann

    Present address: Current address: Roche Pharma Research, Penzberg, Germany.,

  2. G Tiller and H Laumen: These authors contributed equally to this work.

Authors and Affiliations

  1. Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Technische Universität München, Freising, Germany

    G Tiller, H Laumen, T Skurk & H Hauner

  2. Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany

    P Fischer-Posovszky, M Keuper & M Wabitsch

  3. Xantos Biomedicine AG, München, Germany

    A Finck, U Brinkmann & D Link

Authors
  1. G Tiller
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  9. H Hauner
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Corresponding author

Correspondence to H Hauner.

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Competing interests

UB, DL and AF were previously employed by Xantos Biomedicine AG, which in part financially supported the Else Kröner-Fresenius-Center for Nutritional Medicine for GT. The remaining authors declare no conflict of interest.

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Tiller, G., Laumen, H., Fischer-Posovszky, P. et al. LIGHT (TNFSF14) inhibits adipose differentiation without affecting adipocyte metabolism. Int J Obes 35, 208–216 (2011). https://doi.org/10.1038/ijo.2010.126

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  • DOI: https://doi.org/10.1038/ijo.2010.126

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