Measurement of trace elements in post-mortem human visceral and subcutaneous adipose tissues

Abstract

Chronic exposure to heavy metals is a public health burden to the intense industrial mining worldwide. Although several studies investigated the blood physiological concentrations of trace elements in the general population [1] , [2] , very limited information is available on chronic organ accumulation, which is of great relevance to explore the potential impact of trace elements on tissue function. Of note, exposure to trace elements (i.e Zn, Cd, Hg, and Pb) has been associated with increased risk of obesity and its complications, such as type 2 diabetes (T2DM) [3] , but the molecular mechanisms underlying such effects are still unclear. Here, we evaluate the levels of accumulation of five trace elements (Cd, Hg, As, Zn and Pb) in human visceral (VAT) and sub-cutaneous adipose tissue (SAT), two depots playing an opposite role in the development of obesity-related complications. The concentration of Cd, Hg, As, Zn and Pb was measured by ICP-MS (Agilent 7700 Series) in 100 anonymized samples of VAT (omental) and SAT (abdominal) collected during autopsy in our center. For each case the postmortem interval was known. Other information included age, sex, body mass index (BMI), and smoking habit. For group comparisons, Mann–Whitney U test was performed. We first evaluated the impact of postmortem interval on trace element tissue concentration and found only a weak correlation (ρs = 0.25, P = 0.02) between Cd levels in VAT and PM interval and no correlation for As, Hg, Zn, and Pb ( P = 0.15, P = 0.97, P = 0.96, and P = 0.95), suggesting that adipose tissue is not strongly impacted by post-mortem redistribution of the studied elements. The antemortem bioaccumulation of trace elements varies between the two adipose depots and is significantly higher in VAT for Cd, Hg, As and Zn ( P < 0.0001), while Pb was significantly higher in SAT compared to VAT ( P = 6.9E −7 ). Positive correlations were observed between VAT and SAT levels of Cd (ρs = 0.83, P < 10 −15 ), Hg (ρs = 0.44, P = 9E −6 ), Zn (ρs = 0.46, P = 3E −6 ), and As (ρs = 0.85, P < 10 −15 ), but not Pb (ρs = 0.12, P = 0.25). Finally, we explored the link between BMI and VAT trace element levels by logistic regression. Notably, in lean subjects (BMI < 25) and in obese subjects (BMI > 30), we found a significant association between BMI and VAT concentration of Zn (OR = 0.33, 95% CI: 0.13 to 0.79, P = 0.013), Cd (OR = 0.29, 95% CI: 0.11 to 0.74, P = 0.009), Pb (OR = 0.12, 95% CI: 0.23 to 0.67, P = 0.016), and Hg (OR = 0.42, 95% CI: 0.19 to 0.93, P = 0.032), after adjustment by age, sex, smoking status and post-mortem delay. No association was observed with As concentration. Our study profiles for the first time the physiological range of accumulation of Cd, Hg, As, Zn and Pb in two functionally different adipose tissue depots. Moreover, in agreement with previous studies, we highlight an association between trace element levels and obesity. To further understand the impact of these trace elements on adipose tissue function, future analyses will be performed in larger human cohorts and will include additional metabolic, genetic and toxicological parameters.