The stimulation of tumor necrosis factor and inhibition of glucose transport and lipoprotein lipase in adipose cells by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

2,3,7,8,-Tetrachlorodibenzo-o-dioxin (TCDD) is found throughout the environment in industrialized countries, and most people have had some exposure, TCDD has very high lipid solubility and is concentrated in adipose tissue. Because an epidemiologic association between TCDD exposure and diabetes has been described, we examined the effects of TCDD in adipocytes. The addition of TCDD to 3T3-F442a cells, both at the initiation of differentiation and after cells were fully differentiated, resulted in a 2-fold increase in the secretion of tumor necrosis factor (TNF). When added during differentiation, there was also a 25% decrease in lipid accumulation. In addition to the stimulation of TNF, TCDD affected glucose transport and lipoprotein lipase (LPL) activity. When added to cultures of cells that were undergoing differentiation, TCDD inhibited total 2-deoxyglucose transport in a dose-dependent fashion, with 50% inhibition of glucose transport when added to cultures for 48 hours at 5 nmol/L TCDD. In addition, when cells were exposed to 50 nmol/L TCDD for 48 hours, there was a 40% reduction in LPL activity. Thus, the addition of TCDD to adipocyte cultures resulted in an increase in TNF secretion and a decrease in glucose transport and LPL activity. Because TCDD is concentrated in adipose tissue, these studies provide a possible physiologic mechanism for epidemiologic studies that link dioxin to diabetes.