Oral gavage of oleoyl‐oestrone has a stronger effect on body weight in male Zucker obese rats than in female

Abstract

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.

Effect of oral oleoyl-estrone treatment on plasma lipoproteins and tissue lipase activities of Zucker lean and obese female rats

“…20 The increase in muscle lipoprotein lipase, and the decreases in hepatic lipase and WAT lipoprotein lipase induced by oleoyl-estrone treatment changed the main site for lipoprotein-carried lipid disposal in the obese rat: from WAT and liver to skeletal muscle. This shift also helped to normalize plasma lipids, 10 and lipoprotein size and lipid content 14 in oleoyl-estrone-treated animals.…”

“…20,33 Oleoyl-estrone treatment decreased triacylglycerol and total cholesterol plasma levels, in agreement with previous findings. 10,16 However, the changes elicited by oleoyl-estrone were different in lean and in obese rats. In the former, most of the change was attributable to HDL, the lipid content of which decrease by almost two thirds, with only limited change, if any, in the other plasma lipoprotein fractions.…”

“…8 This is accomplished by decreasing appetite but maintaining energy expenditure. 5 The loss of fat is dosedependent, 9 and independent of sex, 10 and of the mode of administration, ie continuous i.v. injection, 5 oral gavage 9,10 or dispersed in the food.…”

“…5 The loss of fat is dosedependent, 9 and independent of sex, 10 and of the mode of administration, ie continuous i.v. injection, 5 oral gavage 9,10 or dispersed in the food. 8 A large proportion of oral oleoylestrone is absorbed unaffected by the digestive process and transferred to lipoproteins.…”

Oleoyl-estrone is a precursor of an estrone-derived ponderostat signal

“…Treatment with OE is more effective in male than in female rats [9] and induces weight losses even under treatment with cafeteria diet [10] or other hyperlipidic diets [4,11]. A peculiarity of OE treatment is the permanent loss of fat, suggesting a role as ponderostat signal for the estrone ester [12].…”