Dehydroepiandrosterone alters lipid profiles in Zucker rats

Abstract

High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean rats (approximately 0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P < 0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.

Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model

“…This observation suggests that gaining less body weight by DHEA treatment may be responsible for lower liver steatosis [20]. Some studies reported that DHEA can decrease body weight gain [8,21,22]. …”

Effects of Dehydroepiandrosterone on Oleic Acid Formation in the Liver of Rats, Mice and Guinea Pigs

“…DHEA is considered to act as a reservoir for the subsequent production of sex steroids and a buffer hormone that changes state dependency by interacting with other hormones. There is a growing interest in DHEA with regard to clinical and pharmacological importance in fat metabolism (1,2), atherosclerosis (3,4), diabetes (5,6), hypertension (7,8) and cancer prevention (9,10). Recently, our study demonstrated that the treatment of rats with DHEA markedly increased the activity of stearoyl-coenzyme A (CoA) desaturase in the liver, leading to an increase in the content of 18:1 D in hepatic lipids (11).…”

Dehydroepiandrosterone Treatment Alters Lipid/Phospholipid Profiles of Rat Brain and Liver Mitochondria

“…Changes in the fatty acid composition of serum, hepatic and adipose lipids in lean and obese Zucker rats, following treatment with DHEA have been reported by Abadie et al (2000). Mc Intosh et al (1999) reported decreased serum and liver lipid contents following DHEA treatment.…”

“…Abadie et al 2000 reported that treatment with DHEA for 30 days resulted in significant alteration of fatty acid profiles of serum, hepatic and adipose lipid components in lean and obese Zucker rats. DHEA feeding also resulted in increased proportion of arachidonic acid in total lipids and decreased oleic acid in soleus as well as cardiac muscle (Abadie et al, 2001;Imai et al, 1999) reported that the increase in hepatic content of oleic acid induced by DHEA in the rat was attributable to the induction of stearoylCoA desaturase.…”