Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism.

Abstract

Obesity is thought to result from poor diet and insufficient exercise. An additional factor may be endocrine-disrupting environmental chemicals that contaminate the air, water, and food supply. We tested the hypothesis that a class of lipid-soluble flame retardant chemicals known to accumulate in adipose tissue, polybrominated diphenyl ethers (PBDEs), disrupts insulin and isoproterenol sensitivity of isolated rat adipocytes. Six-week-old Sprague-Dawley rats were gavaged daily with 14 mg/kg body weight (BW) pentabrominated diphenyl ether (penta-BDE) in corn oil (n = 24) or corn oil alone (n = 24). At 2 and 4 weeks of treatment, epididymal fat pad adipocytes were isolated, and isoproterenol-stimulated lipolysis, insulin-stimulated glucose oxidation, and adipocyte size were measured. There was no alteration in adipocyte metabolism after 2 weeks of in vivo penta-BDE treatment, but after 4 weeks of treatment, adipocytes averaged a 30% increase in isoproterenol-stimulated lipolysis and a 59% decrease in insulin-stimulated glucose oxidation, compared with control. There were no differences in average rat BW and adipocyte size between treated and control rats, but plasma total thyroxine level in 2- and 4-week treated rats was 30% of control. Daily exposure of rats to 14 mg/kg BW penta-BDE for 4 weeks has no effect on animal or adipocyte size but significantly alters insulin and isoproterenol-stimulated metabolism of isolated adipocytes. These alterations, hallmark features of metabolic obesity, suggest the need for further research on the contribution of lipid-soluble, endocrine-disrupting environmental chemicals to the obesity epidemic.