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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 494-504 |
| Number of pages | 11 |
| Journal | BioFactors |
| Volume | 39 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jul 1 2013 |
| Externally published | Yes |
Fingerprint
Keywords
- Alternative test method development
- Aryl hydrocarbon receptor
- Dioxins
- Insulin resistance
- Metabolic syndrome
- Mitochondrial dysfunction
- Obesity
- POPs
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Clinical Biochemistry
Cite this
Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction. / Park, Wook Ha; Jun, Dae Won; Kim, Jin Taek; Jeong, Jae Hoon; Park, Hyokeun; Chang, Yoon Seok; Park, Kyong Soo; Lee, Hong Kyu; Pak, Youngmi Kim.
In: BioFactors, Vol. 39, No. 4, 01.07.2013, p. 494-504.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction
AU - Park, Wook Ha
AU - Jun, Dae Won
AU - Kim, Jin Taek
AU - Jeong, Jae Hoon
AU - Park, Hyokeun
AU - Chang, Yoon Seok
AU - Park, Kyong Soo
AU - Lee, Hong Kyu
AU - Pak, Youngmi Kim
PY - 2013/7/1
Y1 - 2013/7/1
N2 - 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.
AB - 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.
KW - Alternative test method development
KW - Aryl hydrocarbon receptor
KW - Dioxins
KW - Insulin resistance
KW - Metabolic syndrome
KW - Mitochondrial dysfunction
KW - Obesity
KW - POPs
UR - http://www.scopus.com/inward/record.url?scp=84881662568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881662568&partnerID=8YFLogxK
U2 - 10.1002/biof.1092
DO - 10.1002/biof.1092
M3 - Article
C2 - 23361953
AN - SCOPUS:84881662568
VL - 39
SP - 494
EP - 504
JO - BioFactors
JF - BioFactors
SN - 0951-6433
IS - 4
ER -