Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs.

Marike M Leijs,Kees Olie,Gavin W Ten Tusscher,Wim M C Van Aalderen,Janna G Koppe,Thomas Vulsma,Pim De Voogt,Juliette Legler,Umberto Simeoni

doi:10.1371/journal.pone.0184006

Marike M Leijs, Kees Olie + Show 7 more

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https://doi.org/10.1371/journal.pone.0184006

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Abstract

ObjectivesDioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life.Study designIn The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS.ResultsPrenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI.Discussion/ConclusionThis study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

Highlights

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) belong to the group of most hazardous environmental toxicants
Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence
Current serum levels of polychlorinated dibenzo-pdioxins (PCDD)/Fs and total TEQ were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of polybrominated diphenylethers (PBDE)

Summary

Introduction

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) belong to the group of most hazardous environmental toxicants. The genomic (or classical action) pathway is interrelated with the retinoic acid (RA) signalling pathway [5]. Binding with this receptor mediates many pathological processes like teratogenesis and tumor promotion as well as disturbances in many metabolic processes in humans and animals [6]. The non-genomic pathway has been identified to play an important role in the inflammatory action of dioxins (intracellular Ca2+ concentration, enzymatic activation of phospholipase A2 and Cox2) [7] as well as other processes like insulin secretion, fat storage, liver damage and tumorigenesis, and is potentially regulated by miRNAs [8]. Dioxin-like compounds as well as PCBs have been proven to be endocrine disrupters by a variety of mechanisms [9,10,11]

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