title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
authors.forename: T H
authors.initials: TH
authors.lastname: Tu
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
authors.forename: C-S
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: I S
authors.initials: IS
authors.lastname: Nam-Goong
authors.affiliation: Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: C W
authors.initials: CW
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: E S
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: Y I
authors.initials: YI
authors.lastname: Kim
authors.affiliation: University of Ulsan College of Medicine Biomedical research Center, Ulsan, South Korea.
authors.forename: J I
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Graduate School of Agriculture, Kyoto University, Uji, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Graduate School of Agriculture, Kyoto University, Uji, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Food and Nutrition, Yonsei University, Seoul, South Korea.
authors.forename: T
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Food Science and Nutrition, and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon, South Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Yoon Park
authors.affiliation: Department of Food Science and Nutrition, Center for Food & Nutritional Genomics, Kyungpook National University, Deagu, South Korea.
authors.forename: M-S
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
authors.forename: R
authors.initials: R
authors.lastname: Yu
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D015992:Body Mass Index; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D012995:Solubility; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*
chemical_list: D053330:4-1BB Ligand; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9