Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zuckerrats is not due to changes in serum entrostatin-like immunoreactivity

To understand the mechanism(s) of appetite modulation by DHEA, we have unde rtaken a series of studies to examine the effects of DHEA on neurotransmitt ers and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known t o cause selective diminution in fat intake. Four-week-old lean (fa/+) and o bese (fa/fa) Zucker rats were divided into control and treatment groups. DH EA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collec ted from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001 ) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and b ody weight, we examined the effect of caloric intake and body weight on E-L I levels. Serum ELI levels were lower in the obese DHEA-treated group compa red to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/ - 185 ng/mL, it = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had sign ificantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could b e due to increased peptide metabolism, the rate of disappearance of endogen ous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was ev aluated. The results show an attenuation of peptide metabolism in serum fro m DHEA-treated rats, a finding contrary to our expectations. In summary, DH EA treatment lowers serum E-LI levels both in lean and obese Zucker rats. T his decrement in peptide level is not secondary to changes in body weight o r caloric intake due to DHEA, or due to altered serum peptide metabolism. A lthough DHEA appears to be a potent modulator of E-LI levels, the relations hip between DHEA and E-LI in relation to appetitive behavior remains to be clarified. (C) 2000 Elsevier Science Inc. All rights reserved.