Abstract
Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 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 liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) levels. Female Zucker rats were randomly assigned to either a control diet or a control diet with DHEA supplementation for 155 days. Livers were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that DHEA-fed rats had significantly less liver steatosis (p < 0.001) than control-fed rats and gained less weight (p < 0.001). 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 DHEA feeding can protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in an obese breast cancer rat model.
Highlights
More than two-thirds (68.5%) of American adults are either overweight or obese [1]
When liver weight was expressed as percent of body weight, DHEA-fed rats had significantly higher liver weight than control rats (p < 0.001)
We reported that while only 55% of the obese control rats developed mammary tumors, there were no mammary tumors found in the DHEA-fed rats (p < 0.001)
Summary
More than two-thirds (68.5%) of American adults are either overweight or obese [1]. In the US, 34.9%are obese, and 6.4% are extremely obese (grade 3 obesity) [1]. More than two-thirds (68.5%) of American adults are either overweight or obese [1]. More than 1.9 billion adults are overweight, and over 600 million adults are obese [2]. Obesity is associated with serious health problems such as cardiovascular disease, type 2 diabetes, certain types of cancers, hyperlipidemia, and liver steatosis [3]. It has been shown that DHEA has potential as an anti-cancer agent and anti-obesity supplement [4]. Levels of serum DHEA or the DHEA metabolite DHEA sulfate (DHEA-S) were significantly inversely related to abdominal obesity [5,6]. Studies in postmenopausal women reported that DHEA-S did not protect against obesity [7]. In laboratory animals (rats and mice), DHEA feeding reduced fat accumulation in both genetic- and diet-induced obesity, and had protective effects against insulin resistance induced by a high-fat diet [8,9]
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