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ASSESSING TCDD WASTING SYNDROME IN AN IN VIVO OBESITY MODEL
Citation:
LAMERRILL, M. A., L. S. BIRNBAUM, AND D. THREADGILL. ASSESSING TCDD WASTING SYNDROME IN AN IN VIVO OBESITY MODEL. Presented at Society of Toxicology Annual Meeting, San Francisco, CA, March 25 - 29, 2007.
Description:
TCDD is a by-product of incineration commonly found as a microcontaminant in the food supply. The TCDD wasting syndrome, characterized by prolonged weight loss, has been examined for decades. Much of this work has focused on high dose in vivo and in vitro studies. This body of work suggests that TCDD inhibits adipogenesis and that these effects are not rescued by high fat diet. We hypothesized that a low dose of TCDD during a developmentally sensitive window would induce the TCDD wasting syndrome in mice on high and low fat diets. FVB/NJ females were dosed with 1 µg/kg TCDD or vehicle on gestational day 12.5. At birth, cages were placed on standardized low or high fat diets. Body weights were measured weekly through weaning and monthly thereafter. Percent body fat was measured at 5 weeks, 3 and 6 months of age. Fasting blood glucose was measured at 5 weeks, 4 and 6 months of age. Body weights were higher in mice on high fat diet compared to low fat diet throughout the lifespan evaluated. However, TCDD exposure did not alter their body weights. High fat diet increased percent body fat at 3 months and blood glucose at 4 months. Again TCDD had no effect on these measures. In summary developmental low dose TCDD has no overall impact on classic wasting syndrome phenotypes, both during the time period in which TCDD is expected to be in the tissue and long after it is expected to be cleared. This longitudinal study of the affect of low dose TCDD on the wasting syndrome suggests that the wasting syndrome is a high dose phenomenon.