SAT-553 - Effects of Developmental Exposure to per- and Polyfluoroalkyl Substances (PFAS) and Western Diet on Rat Feeding Behavior and Glucose Metabolism

Per- and polyfluoroalkyl substances (PFAS) are a class of widespread persistent organic pollutants associated with immune, metabolic and neural dysfunction in humans. These processes are also impacted by exposure to the ‘Western’ high -sugar and -fat diet, however, interacting effects of PFAS exposure and diet on metabolic regulation have not been tested. Exposure to PFAS is high during sensitive gestational and neonatal periods of development. Adolescence is also of interest, as nutritional demands shift, eating habits stabilize, and adipocytes mature. This study tests the hypothesis that developmental exposure to PFOS shifts adolescent food preferences and metabolic function in ways that are revealed or exacerbated by dietary challenge and may be sex-dependent. To test this, ten pregnant Sprague Dawley rats were fed perfluorooctane sulfonate (PFOS, 0.5 mg/kg dam BW) or vehicle control (0.5% Tween-80 in water) daily over gestation and lactation. Starting a week after weaning, on postnatal day (P)28, two male and two female pups from each litter received either standard chow food pellets or a western diet plus chow ad libitum for four weeks until euthanasia at the end of adolescence (P56), n = 8-10 in each of eight groups. The western ‘cafeteria’ diet consisted of a three-day rotating menu containing different popular chips, cake, meat, and candy every day. Effects of PFOS exposure, diet, and sex were determined with two and three-way analysis of variance. Sweet preference, measured as intake of sucrose-sweetened or standard water in a two-hour home-cage choice test, was lower in western diet exposed females (F(1,33) = 5.1, p = 0.03), but not males, compared to chow controls, with no statistically significant effects of PFOS. Fat preference, measured in a similar test with high-fat or standard chow pellets, was reduced by PFOS exposure in males (F(1,35) = 5.6, p = 0.02), but not females, without significant effects of diet. Fasted blood glucose (F(1,68) = 45, p < 0.01) and glucose tolerance test area under the curve (F(1,68) = 19, p < 0.01) was greater in western diet animals, with no statistical effect of PFOS. However, PFOS exposed animals showed delays in blood glucose returning to baseline, with higher concentrations at 120 minutes. In females, this was additive to dietary effects (F(1,33) = 6.6, p = 0.01) while in males, western diet did not further increase concentrations beyond that already caused by PFOS exposure (F(1,35) = 8.3, p < 0.01). Taken together, these results affirm effects of PFOS exposure on dysregulated glucose metabolism and raise behavioral effects as possible indicators of PFOS effects on lipid homeostasis and/or as a mechanism of metabolic risk. Moreover, they highlight the importance of testing effects of chemical contaminants in a range of homeostatic states, as ‘two-hits’ over development can better model the human condition and reveal otherwise latent effects.

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