Abstract

Obesity has been an epidemic in the US and world for more than two decades. Obesity is associated with serious health conditions, including type 2 diabetes, cardiovascular disease, certain types of cancers, hyperlipidemia, and liver steatosis. Nonalcoholic fatty liver disease (NAFLD), a major cause of abnormal liver function, is often associated with obesity. Dehydroepiandrosterone (DHEA) is a dietary supplement that is available in many health food stores and has been shown as an anti-cancer agent and anti-obesity supplement. Previously, we reported that obesity promotes 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on mammary tumor development and liver steatosis. Female Zucker rats were randomly assigned and had ad libitum access to water and a diet of either control or diet with DHEA at a concentration of 6 g/kg of diet. All rats were orally gavaged at age 50 days with 65 mg DMBA/kg body weight. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 155 days post-DMBA treatment. Livers and mammary tumors were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that; 1) Obese rats fed the DHEA diet gained significantly less weight than obese control diet rats (P < 0.001) than control-fed rats; 4) DHEA feeding caused significant decreases (p < 0.001) in the serum levels of IGF-1 and IGFBP-3 and significantly increased (p < 0.001) serum levels of DHEA and DHEA-S. Our results suggest that lowering body weight can protect against DMBA-mammary tumors and liver steatosis.

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