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Integrative Biology

Levels of 4-1BB transcripts and soluble 4-1BB protein are elevated in the adipose tissue of human obese subjects and are associated with inflammatory and metabolic parameters

International Journal of Obesity volume 38, pages 1075–1082 (2014)Cite this article

Subjects

Abstract

Background:

4-1BB, a member of the TNF receptor superfamily, has a role in various inflammatory pathologies through its interaction with 4-1BB ligand. We previously demonstrated that it participates in initiating and promoting obesity-induced adipose inflammation in a rodent model.

Objective:

In this study, we examined whether 4-1BB is related to obesity-induced adipose inflammation and metabolic parameters in humans.

Methods:

A total of 50 subjects, 25 obese (body mass index (BMI)⩾25 kg m−2) and 25 lean (BMI<23 kg m−2) participated in the study. The levels of 4-1BB transcripts and soluble 4-1BB protein (s4-1BB) in subcutaneous adipose tissue were measured by quantitative real-time PCR and enzyme-linked immunosorbent assay, respectively. Inflammatory and metabolic parameters were measured by enzymatic analysis and immunoassay.

Results:

Obese subjects had higher levels of both 4-1BB transcripts and s4-1BB protein in subcutaneous adipose tissue than lean controls, and the levels were correlated with BMI and the expression of inflammatory markers, as well as with serum metabolic parameters. Moreover, s4-1BB was released from human adipocytes, and elicited chemotactic responses from human monocytes/T cells as well as enhancing their inflammatory activity, indicating that it may promote human adipose inflammation.

Discussion:

Our data demonstrate that elevated levels of 4-1BB transcripts and s4-1BB in adipose tissue are closely associated with obesity-induced inflammation and metabolic dysregulation. They suggest that both 4-1BB transcripts and s4-1BB could serve as novel biomarkers and/or therapeutic targets for obesity-induced inflammation and metabolic syndrome in humans.

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Acknowledgements

This work has supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No.2012R1A2A4A01002702), and an NRF grant funded by the Korean government (MSIP) (No.2008-0062618).

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Authors and Affiliations

  1. Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea

    T H Tu, C-S Kim, J-H Kang & R Yu

  2. Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

    I S Nam-Goong, E S Kim & Y I Kim

  3. Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

    C W Nam

  4. University of Ulsan College of Medicine Biomedical research Center, Ulsan, South Korea

    J I Choi

  5. Graduate School of Agriculture, Kyoto University, Uji, Japan

    T Kawada & T Goto

  6. Department of Food and Nutrition, Yonsei University, Seoul, South Korea

    T Park

  7. Department of Food Science and Nutrition, and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon, South Korea

    J H Yoon Park

  8. Department of Food Science and Nutrition, Center for Food & Nutritional Genomics, Kyungpook National University, Deagu, South Korea

    M-S Choi

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Tu, T., Kim, CS., Kang, JH. et al. Levels of 4-1BB transcripts and soluble 4-1BB protein are elevated in the adipose tissue of human obese subjects and are associated with inflammatory and metabolic parameters. Int J Obes 38, 1075–1082 (2014). https://doi.org/10.1038/ijo.2013.222

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