Zucker obese rats store less acyl-estrone than lean controls

OBJECTIVE: To measure acyl-estrone levels in the plasma of Zucker obese rats. If these are lower than expected on the basis of their body-fat content, as observed in morbidly obese humans, this might provide a possible link relating obesity and low body estrone levels. We also examined the effect of pharmacological treatment with oral oleoyl-estrone on the accumulation of estrone. DESIGN: Undisturbed Wistar, Goto-Kakizaki and Zucker (lean Fa/?and obese fa/fa) rats were used to determine the relation between circulating acyl-estrone and body lipids, as well as the total body estrone/lipid ratios. One group of Wistar rats was used to measure the effect of oral gavages of oleoyl-estrone (from 0 to 20 mumol/kg/day) for 10 days on the body content of estrone. MEASUREMENTS: Body weight change and food intake. Total estrone intake, estrone accrual and excretion (by difference) in rats receiving oleoyl-estrone. Total body lipid and estrone. Circulating acyl-estrone levels. RESULTS: In lean rats (Wistar, Zucker and Goto-Kakizaki) there was a direct relation between body lipid content and circulating acyl-estrone; this relation was not found in Zucker obese rats. The estrone/lipid mass ratio was in a similar range in lean rats, but obese animals showed much lower values. Wistar rats receiving pharmacological doses of oleoyl-estrone did not accumulate significant amounts of estrone, but excreted almost all the estrone ingested. CONCLUSIONS: The pharmacological administration of acyl-estrone to rats does not result in the accrual of estrone within a wide range of doses, which confirms the safety of this compound. In rats there is a similar relation between the percentage of body lipids and circulating acyl-estrone to that found in humans. Likewise, obese rats showed lower levels of acyl-estrone than expected. The total content of estrone in the bodies of obese rats was also lower than expected from their high lipid content, which suggests that obese rats are deficient in acyl-estrone.