Superfund Research Program
Polychlorinated Biphenyls, Nutrition and Diabetes
Project Leader: Lisa A. Cassis
Grant Number: P42ES007380
Funding Period: 2005-2019
Final Progress Reports
Obesity is a common problem in the U.S. that promotes the development of type 2 diabetes. Thus, obese people strive to lose weight through diets or exercise. Because they are lipophilic, polychlorinated biphenyls (PCBs) accumulate in fat, with greater body burdens in obese subjects. During weight loss, PCBs are released from fat stores. The researchers found that this release can blunt the benefits of weight loss to improve glucose homeostasis. During the current period they completed studies determining (1) the role of adipocyte aryl hydrocarbon receptors (AhR) in harmful effects of PCBs on glucose homeostasis in male and female mice during weight loss, (2) whether reservatrol, a polyphenol with AhR blocking abilities, can improve glucose homeostasis during weight loss in male and female obese mice exposed to PCB77. They also determined if effects of reservatrol were through adipocyte AhR. Major findings are:
- Deletion of AhR from adipocytes promotes obesity and impairs glucose homeostasis in male, but not female mice.
- Resveratrol increases weight loss and improves glucose homeostasis in obese male, but not female mice.
- Effects of resveratrol are independent of adipocyte AhR.
- Males have higher plasma PCB77 levels than females, while females have higher reservatrol levels than males.
These results suggest sex differences in effects of adipocyte AhR on weight gain and loss, plasma levels of PCBs and resveratrol, and in the ability of resveratrol to improve glucose homeostasis during weight loss in PCB77-exposed mice.