Association between Exposure to p,p'-DDT and Its Metabolite p,p'-DDE with Obesity: Integrated Systematic Review and Meta-Analysis

Abstract

Background: The prevalence of obesity is increasing in all countries, becoming a substantial public health concern worldwide. Increasing evidence has associated obesity with persistent pollutants such as the pesticide DDT and its metabolite p,p'-DDE.

Objectives: Our objective was to systematically review the literature on the association between exposure to the pesticide DDT and its metabolites and obesity to develop hazard identification conclusions.

Methods: We applied a systematic review-based strategy to identify and integrate evidence from epidemiological, in vivo, and in vitro studies. The evidence from prospective epidemiological studies was quantitatively synthesized by meta-analysis. We rated the body of evidence and integrated the streams of evidence to systematically develop hazard identification conclusions.

Results: We identified seven epidemiological studies reporting prospective associations between exposure to p,p'-DDE and adiposity assessed by body mass index (BMI) z-score. The results from the meta-analysis revealed positive associations between exposure to p,p'-DDE and BMI z-score (β=0.13 BMI z-score (95% CI: 0.01, 0.25) per log increase of p,p'-DDE). Two studies constituted the primary in vivo evidence. Both studies reported positive associations between exposure to p,p'-DDT and increased adiposity in rodents. We identified 19 in vivo studies and 7 in vitro studies that supported the biological plausibility of the obesogenic effects of p,p'-DDT and p,p'-DDE.

Conclusions: We classified p,p'-DDT and p,p'-DDE as "presumed" to be obesogenic for humans, based on a moderate level of primary human evidence, a moderate level of primary in vivo evidence, and a moderate level of supporting evidence from in vivo and in vitro studies. https://doi.org/10.1289/EHP527.

Figure 1.

Flow chart for rating the quality and integration of evidence from human and animal evidence, and the judgments of primary and supporting evidence for hazard identification conclusions.

Figure 2.

Flow chart of the systematic review process.

Figure 3.

Forest plot of the association between exposure to p,p′-DDE with BMI-z from human prospective studies, stratified by exposure units (lipid weight and wet weight). The effect size estimate is the adjusted coefficient regression ($\mathrm{\beta }$) with 95% confidence intervals (units in BMI z-score per log increase of p,p′-DDE) for combined gender (males and female) unless the strata is specifically reported in the cohort label: (F) females or (M) males. Cohorts: CHAMACOS, Center for the Health Assessment of Mothers and Children of Salinas; EYHS, Danish part of the European Youth Heart Study; FLEHS I, first Flemish Environment and Health Study; RMCC, Rhea Mother–Child Cohort; INMA-Sabadell, Infancia y Medio-Ambiente Child and Environment birth cohort. Countries: GL, Greenland; SK, Warsaw Poland; UA, Ukraine; US, United States. Age: age at outcome assessment.

Figure 4.

Forest plot of the associations between exposure to p,p′-DDT and p,p′-DDE and (A) energy balance, (B) circulating adipokines, (C) abnormal liver lipids, and (D) abnormal blood lipids from in vivo studies. Symbols: upward-pointing triangle, increase effect; downward-pointing triangle, decrease effect; circle, no statistical effect. Upward-pointing triangle means adversity of the health effect. Abbreviations: CBA, conjugated bile acids; CHO, cholesterol; DPC, day post-coitus; F, females; FAs, fatty acids; GD, gestational day; HFD, high-fat diet; LE, lipogenic enzymes; LW, liver weight; M, males; NS, no specified; PG, parental generation; PHO, phospholipids; PND, postnatal day; SD, Sprague-Dawley; T, temperature; TAG, triacylglycerol; TL, total lipids; TnG, transgenerational. Doses were approximated to the daily body weight basis using the conversion factors specified in Table S22.

Figure 5.

Forest plot of the association between exposure to p,p′-DDT and p,p′-DDE and (A) adipogenic differentiation, (B) expression of metabolic regulators, and (C) adipokines from in vitro studies. Symbols: upward-pointing triangle, increase effect; downward-pointing triangle, decrease effect; circle, no statistical effect. Upward-pointing triangle means adversity of the health effect. Abbreviations: ATGL, adipose triglyceride lipase; CEBP enhancer-binding protein; Fabp4, Fatty acid binding protein 4; Fasn, fatty acid synthase; Insig1, Insulin-induced gene-1; LpL, lipoprotein lipase; PPAR, peroxisome proliferator-activated receptor; Srebf1, sterol regulatory element-binding protein 1c.