Oral treatment with oleoyl-estrone resulted in the specific dose-related loss of fat reserves with little change to other metabolic parameters. These results agree with the postulated role of oleoyl-estrone as a ponderostat signal.
OBJECTIVE: To determine whether the slimming effects of treatment with oleoyl-estrone (OE) in liposomes of normal and obese rats are permanent, or disappear as soon as the treatment with the drug ceased. This study was devised to gain further knowledge on the postulated role of OE as a ponderostat signal, evaluating whether (in addition) it can lower the ponderostat setting of the rat. DESIGN: The rats were infused for 14 d (using osmotic minipumps) with oleoyl-estrone in liposomes at a dose of 3.5 m mmolakg Á Á d, and were studied up to one month after the treatment ceased. SUBJECTS: Young adult lean controls (CL) or treated (TL) and obese controls (CO) or treated (TO) Zucker rats. MEASUREMENTS: Energy balance, blood glucose, liver glycogen, plasma insulin, leptin corticosterone, ACTH and estrone (free and total) concentrations, and expression of the OB gene in white adipose tissue (WAT). RESULTS: The loss of body weight caused by OE was recovered quickly in the TO, which gained weight at the same rate as the CO. TL rats, however remained at the low weight attained for one month after the treatment ceased. However, no differences were observed in calculated energy expenditure (EE) between the TL and TC rats once treatment had stopped. In TL and TO rats, liver glycogen concentrations decreased to normal shortly after treatment ceased, and leptin expression and concentrations remained normal and unchanged after the end of OE treatment. In TO rats, plasma glucose, insulin and leptin were lower than in the CO. Total estrone concentrations decreased rapidly in TL rats and more slowly in the TO, and free estrone followed a similar pattern. CONCLUSION: Continuous infusion of liposomes loaded with OE resulted in a decreased energy intake (EI), maintenance of EE and the utilization of body fat reserves in lean and obese rats alike. This process ended in obese rats as soon as the infusion ceased, so that even when the levels of free and total estrone in plasma remained high, there was a marked (and relatively fast) shift toward the basal situation, which translated into an increase in EI, maintenance of estimated EE and a marked buildup of energy stores. In lean rats, the effects of OE on leptin concentrations and OB gene expression persisted after infusion ended.
The widely distributed estrone esters in food and their relatively high concentrations may result in high free hormone intakes in humans. The continued and massive intake of estrone may enhance tissue deposition and lead to obesity.
This study was carried out to determine the effect of sex and oral administration of oleoyl-oestrone on body weight of 12-week-old female and male Zucker obese (fa/fa) rats initially weighing 350-380 g and 405-420 g, respectively. The rats were maintained in standard conditions and given a daily oral gavage of 0.2 ml oleoyl-oestrone dissolved in sunflower oil at a dose of 10 micromol/kg/day for 10 days, and their body weight and food intake was monitored. They were then killed, and their carcass composition (water, lipid, protein and total energy), liver lipids and glycogen and plasma chemistry, insulin, free and total oestrone were measured. Oral administration of oleoyl-oestrone via gavage resulted in significant losses of fat, energy and-ultimately-weight. Treatment with oleoyl-oestrone decreased food intake; the energy expenditure was kept close to that of controls at the expense of internal fat stores. Nevertheless, body protein and plasma metabolite homeostasis were preserved. The slimming effects were more marked in males than in females. Treatment increased circulating acyl-oestrone and reduced to normal levels the high insulin observed in controls. Treatment of genetically obese rats with a daily oral gavage of oleoyl-oestrone resulted in the loss of fat reserves with little modification of other metabolic parameters, except for lower plasma glucose and insulin levels. The results suggest that oleoyl-oestrone, in addition to its slimming effects may be effective as an antidiabetic agent in type 2 diabetes.
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