Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hoppe
Andrea A
AA
Department of Animal and Nutritional Sciences, University of New Hampshire, Kendall Hall, 129 Main St., Durham, NH 03824, USA.
Carey
Gale B
GB
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010647:Phenyl Ethers / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D007004:Hypoglycemic Agents; D007328:Insulin; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C086401:pentabromodiphenyl ether; D005947:Glucose; D007545:Isoproterenol