Chlorinated Persistent Organic Pollutants, Obesity, and Type 2 Diabetes

Abstract

Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in adipose tissue.Recent human evidence links low-dose POPs to an increased risk of type 2 diabetes (T2D).Because humans are contaminated by POP mixtures and POPs possibly have nonmonotonic dose-response relations with T2D, critical methodological issues arise in evaluating human findings.This review summarizes epidemiological results on chlorinated POPs and T2D, and relevant experimental evidence.It also discusses how features of POPs can affect inferences in humans.The evidence as a whole suggests that, rather than a few individual POPs, background exposure to POP mixtures-including organochlorine pesticides and polychlorinated biphenylscan increase T2D risk in humans.Inconsistent statistical significance for individual POPs may arise due to distributional differences in POP mixtures among populations.Differences in the observed shape of the doseresponse curves among human studies may reflect an inverted U-shaped association secondary to mitochondrial dysfunction or endocrine disruption.Finally, we examine the relationship between POPs and obesity.There is evidence in animal studies that low-dose POP mixtures are obesogenic.However, relationships between POPs and obesity in humans have been inconsistent.Adipose tissue plays a dual role of promoting T2D and providing a relatively safe place to store POPs.Large prospective studies with serial measurements of a broad range of POPs, adiposity, and clinically relevant biomarkers are needed to disentangle the interrelationships among POPs, obesity, and the development of T2D.Also needed are laboratory experiments that more closely mimic real-world POP doses, mixtures, and exposure duration in humans.(Endocrine Reviews 35: 557-601, 2014) I. Introduction II.Human Evidence Linking POPs and T2D A. What are POPs?B. Earlier puzzling findings linking POPs and T2D C. Recent evidence linking POPs and T2D: cross-sectional and case-control studies D. Reverse causality due to disease progression bias E. Prospective evidence linking POPs and T2D III.Experimental Evidence Linking POPs and T2D IV.POPs and Obesity A. POPs as obesogens B. Are obesogens unequivocally harmful?C. POPs and inflammation in adipose tissue D. POPs, gut microbiota, and obesity E. Can the obesity paradox be explained by POPs?V. Methodological Issues Crucial for Human Studies A. Issue 1: inverted U-shaped associations B. Issue 2: mixtures C. Issue 3: how can we deal with lipid profiles?VI.Possible Mechanisms A. Traditional endocrine disrupting-related mechanisms B. Mitochondrial dysfunction