PCBs Impair Glucose Homeostasis in Mice
Lisa Cassis, Ph.D.
University of Kentucky
NIEHS Grant P42ES007380
There is growing evidence of that PCB exposure is linked with increased risk for type 2 diabetes. A new mouse study from NIEHS grantees provides insight into how coplanar PCBs affect gene expression and accumulate in body fat in a way that leads to problems with regulating glucose.
Because studies suggest that PCB exposure levels are associated with diabetes even in lean individuals, the researchers initiated studies in mice fed a low fat diet. They also conducted studies in mice made obese from consumption of a high fat diet and in a group of obese mice made to lose weight by switching to the low fat diet. Some mice from all the diet groups received PCB-77, and others served as controls. The researchers measured glucose and insulin tolerance as well as levels of tumor necrosis factor alpha (TNF-α) in adipose (body fat), liver, and muscle tissue. TNF-α is known to contribute to insulin resistance.
The investigators found that coplanar PCBs caused rapid and sustained impairment of glucose and insulin tolerance in the mice fed a low fat diet. PCB-77 increased TNF-α expression in adipose, but not liver or muscle tissue. PCB levels were much higher in the adipose tissue than in the liver or serum. In obese mice, PCB-77 did not affect glucose homeostasis, most likely because the compound was sequestered in adipose lipids. However, when the obese mice lost weight, beneficial effects of weight loss on glucose and insulin tolerance were blunted in the mice administered PCB-77, possibly because losing weight released some of the stored PCBs. This finding may have implications for people trying to lose weight because liberation of PCBs from adipose could have detrimental effects.
In vivo and in vitro experiments revealed that interfering with aryl hydrocarbon receptors (AhR) stopped the effects of PCB-77, thus showing that an AhR-dependent mechanism was involved. PCB-77 is an AhR ligand. The researchers conclude that adipose-specific elevations in TNF-α expression may contribute to impaired glucose homeostasis.
Citation: : Baker NA, Karounos M, English V, Fang J, Wei Yinan, Stromberg A, Sunkara M, Morris AJ, Swanson HI, Cassis LA. 2012. Coplanar Polychlorinated Biphenyls Impair Glucose Homeostasis in Lean C57BL/6 Mice and Mitigate Beneficial Effects of Weight Loss on Glucose Homeostasis in Obese Mice. Environ Health Perspect; doi:10.1289/ehp.1205421 [Online 24 October 2012]
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