Get access

Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction

Authors

  • Wook-Ha Park,

    1. Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea
    2. Department of Neuroscience, College of Medicine, Kyung Hee University, Seoul, Korea
    Search for more papers by this author
    • Wook-Ha Park and Dae Won Jun are contributed equally to this work.

  • Dae Won Jun,

    1. Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea
    Search for more papers by this author
    • Wook-Ha Park and Dae Won Jun are contributed equally to this work.

  • Jin Taek Kim,

    1. Department of Internal Medicine, College of Medicine, Eulji-University, Seoul, Korea
    Search for more papers by this author
  • Jae Hoon Jeong,

    1. Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea
    2. Department of Neuroscience, College of Medicine, Kyung Hee University, Seoul, Korea
    Search for more papers by this author
  • Hyokeun Park,

    1. School of Environmental Science and Engineering, Postech, Pohang, Korea
    Search for more papers by this author
  • Yoon-Seok Chang,

    1. School of Environmental Science and Engineering, Postech, Pohang, Korea
    Search for more papers by this author
  • Kyong Soo Park,

    1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
    Search for more papers by this author
  • Hong Kyu Lee,

    Corresponding author
    1. Department of Internal Medicine, College of Medicine, Eulji-University, Seoul, Korea
    • All correspondence to: Youngmi Kim Pak, Ph.D., Department of Physiology, College of Medicine, Kyung Hee University, #26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Korea; Tel.: +82-2-961-0908; Fax: +82-2-969-6343; E-mail: hkleemd@eulji.ac.kr; or Hong Kyu Lee, M.D., Ph.D., Department of Internal Medicine, College of Medicine, Eulji-University, Seoul 139-872, Korea; Tel: +82-2-970-8458; Fax: +82-2-970-4630; ykpak@khu.ac.kr

    Search for more papers by this author
  • Youngmi Kim Pak

    Corresponding author
    1. Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea
    2. Department of Neuroscience, College of Medicine, Kyung Hee University, Seoul, Korea
    • All correspondence to: Youngmi Kim Pak, Ph.D., Department of Physiology, College of Medicine, Kyung Hee University, #26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Korea; Tel.: +82-2-961-0908; Fax: +82-2-969-6343; E-mail: hkleemd@eulji.ac.kr; or Hong Kyu Lee, M.D., Ph.D., Department of Internal Medicine, College of Medicine, Eulji-University, Seoul 139-872, Korea; Tel: +82-2-970-8458; Fax: +82-2-970-4630; ykpak@khu.ac.kr

    Search for more papers by this author

Abstract

Serum concentrations of environmental pollutants have been positively correlated with diabetes and metabolic syndrome in epidemiologic studies. In turn, abnormal mitochondrial function has been associated with the diseases. The relationships between these variables, however, have not been studied. We developed novel cell-based aryl hydrocarbon receptor (AhR) agonist bioassay system without solvent extraction process and analyzed whether low-dose circulating AhR ligands in human serum are associated with parameters of metabolic syndrome and mitochondrial function. Serum AhR ligand activities were measured as serum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (sTCDDeq) in pM using 10 μL human sera from 97 Korean participants (47 with glucose intolerance and 50 matched controls, average age of 46.6 ± 9.9 years, 53 male and 45 female). sTCDDeq were higher in participants with glucose intolerance than normal controls and were positively associated (P < 0.01) with obesity, blood pressure, serum triglyceride, and fasting glucose, but not with HDL-cholesterol. Body mass index was in a positive linear relationship with serum AhR ligands in healthy participants. When myoblast cells were incubated with human sera, ATP generating power of mitochondria became impaired in an AhR ligand concentration-dependent manner. Our results support that circulating AhR ligands may directly reduce mitochondrial function in tissues, leading to weight gain, glucose intolerance, and metabolic syndrome. Our rapid cell-based assay using minute volume of human serum may provide one of the best monitoring systems for circulating AhR ligands, good clinical biomarkers for the progress of disease and therapeutic efficacy. © 2013 BioFactors, 39(4):494–504, 2013

Ancillary