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

doi:10.1002/biof.1092

Cited by 48 publications

(77 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are several possible mechanisms to link serum AHRT activity and diabetic nephropathy. We have found that serum AHRT activity correlated with its inhibitory function on cell respiration. In the previous report, we showed that serum AHRT activities had a positive correlation with ROS production and a negative correlation with adenosine triphosphate (ATP) levels.…”

Section: Discussionmentioning

confidence: 90%

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Kim

Kim²,

Jun

et al. 2013

J of Diabetes Invest

Self Cite

View full text Add to dashboard Cite

Aims/Introduction: Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity-related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell-based arylhydrocarbon receptor (AhR)-dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes. Materials and Methods: We enrolled diabetic patients with normoalbuminuria (n = 36), microalbuminuria (n = 29), macroalbuminuria (n = 8) and end-stage renal disease (n = 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L). Results: Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 -7.1 pmol/L), macroalbuminuria (37.4 -5.5 pmol/L) and end-stage renal disease (59.1 -20.0 pmol/L) than in subjects with normoalbuminuria (12.7 -5.4 pmol/L; P < 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r = -0.663, P < 0.001), serum creatinine level (r = 0.635, P < 0.001), systolic blood pressure (r = 0.223, P = 0.026), glycated hemoglobim (r = 0.339, P < 0.001) and diabetic duration (r = 0.394, P < 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors. Conclusions: The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy. (J Diabetes Invest,

show abstract

Section: Discussionmentioning

confidence: 90%

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Kim

Kim²,

Jun

et al. 2013

J of Diabetes Invest

Self Cite

View full text Add to dashboard Cite

show abstract

“…We took such "bottom up" approach and tested if subjects with T2DM or metabolic syndrome have higher serum AhR transactivation activity [69]. We developed novel cell-based AhR ligand activity (CALA) assay 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.…”

Section: Biologic Tests For Edcsmentioning

confidence: 99%

Metabolic syndrome and the environmental pollutants from mitochondrial perspectives

Kim

Lee

2014

Rev Endocr Metab Disord

Self Cite

View full text Add to dashboard Cite

The worldwide epidemic of diabetes and metabolic syndrome in the last few decades cannot be fully accounted for only by changes in the lifestyle factors, such as sedentary lifestyle and overeating. Besides genetic factors, there must be other causes to explain this rapid change. They could not be infectious in nature and induce insulin resistance as key biochemical abnormality. Mitochondrial dysfunction could be underlying mechanism behind the insulin resistance, thus metabolic syndrome. Then there have been increasing number of reports suggesting that chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs), especially so-called the persistent organic pollutants (POPs) within the body might be associated with metabolic syndrome. Combining two concepts, we developed new "EDCs-induced mitochondrial dysfunction hypothesis of metabolic syndrome". In this review we suggest that classifying those chemicals into 5 groups might be clinically useful considering their removal or avoidance; POPs, non-persistent organic pollutants, heavy metals, air pollutants and drugs. We will also discuss briefly how those insights could be applied to clinical medicine.

show abstract

“…When mitochondrial function is perturbed, diseases involving energy utilization easily result: obesity and insulin resistance are prototypes of these diseases [190]. Furthermore, mitochondrial abnormalities are associated with intracellular lipid accumulation, insulin resistance and the pathophysiology of type 2 diabetes [187,191–193]. …”

Section: Mechanisms Of Dioxin-induced Beta Cell Dysfunctionmentioning

confidence: 99%

Association of Dioxin and Other Persistent Organic Pollutants (POPs) with Diabetes: Epidemiological Evidence and New Mechanisms of Beta Cell Dysfunction

Tata

2014

IJMS

View full text Add to dashboard Cite

The worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet. For this reason, it has been recently proposed that other “nontraditional” risk factors could contribute to the diabetes epidemics. In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis. In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed.

show abstract

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

Cited by 48 publications

References 40 publications

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Metabolic syndrome and the environmental pollutants from mitochondrial perspectives

Association of Dioxin and Other Persistent Organic Pollutants (POPs) with Diabetes: Epidemiological Evidence and New Mechanisms of Beta Cell Dysfunction

Contact Info

Product

Resources

About