Chronic Exposure to PCBs (Aroclor 1254) Exacerbates Obesity-Induced Insulin Resistance and Hyperinsulinemia in Mice

Abstract

Evidence from recent epidemiological studies has emerged implicating exposure to environmental toxicants as a novel risk factor for the development of type 2 diabetes (T2D) and the metabolic syndrome in the general population. Humans and other organisms in high trophic levels of the food chain consume persistent organic pollutants (POP) through their diet. Few experimental studies demonstrating cause and effect are available and evidence for a direct association between accumulation of POP and T2D is preliminary; however, the possibility exists that lipophilic chemicals that accumulate in fatty tissue may disrupt cellular function and metabolic homeostasis. Chronic exposure of diabetes-prone C57B/6 mice to a polychlorinated biphenyl (PCB) mixture (Aroclor 1254, 36 mg/kg/wk, 20 wk) alone or in combination with high-fat diet impairs carbohydrate metabolism was compared to vehicle-treated control animals. Specifically, PBC exposure was found to produce hyperinsulinemia in both lean and diet-induced obese mice and exacerbated whole-body insulin resistance in obese mice. These changes in carbohydrate metabolism in response to Aroclor 1254 occurred without marked effect on body weight in both lean and obese mice. Our results demonstrate a causative association between PCB exposure and obesity-induced insulin resistance and hyperinsulinemia independent of body weight changes, an observation that contributes to a growing body of evidence suggesting that exposure to environmental pollutants represents a novel risk factor contributing to the diabetes epidemic.

Acknowledgments

Author Alyssa C. Shaw passed away before the submission of this article.

This work was supported by a seed grant from the University of Northern British Columbia. S. L. Gray is a Tier 2 Canada Research Chair in the Integrative Physiology of Diabetes and held a Scholar Award from the Canadian Diabetes Association from 2008–2012 (grant SC-5-08-2495-SG); H. M. Chan is a Tier 1 Canada Research Chair in Toxicology and Environmental Health and is funded by a a National Sciences and Engineering Research Council of Canada, Discovery Grant and a BC Leadership Chair. The authors thank Lydia Troc and Dee Jones of the Northern Health Sciences Centre (NHSC) animal facility and undergraduate research assistant Tamara Charlie for their exceptional technical expertise.