Combined effects of oral oleoyl-estrone and limited food intake on body composition of young overweight male rats

Abstract

Objective: The combined effects of limited food intake and OE treatment have been analysed in order to determine whether hypocaloric diets enhance the slimming effects of OE on mature overweight male rats. Two levels of dietary limitation at 50 and 25% of a standard intake were established, roughly corresponding to the human LCDs and VLCDs. Design: Wistar male rats (6 weeks old) were made overweight by a cafeteria diet. After transition to standard diet, they were subjected to food restriction: down to 50 or 25% with respect to the transition period. Half the animals were given daily oral gavages of 10 nmol/g oleoyl-estrone (OE), and the rest received only the vehicle during 10 days. Measurements: Changes in weight and body composition: water, lipid, protein or gross energy were determined by comparing the final pool size with that of day 0, calculated from the initial body weight and the composition of untreated rats. Energy and nitrogen balances were estimated. Plasma levels of metabolites and hormones were also measured. Results: OE induced changes in body composition similar to those elicited by a 50% reduction in food, with massive loss of lipid and energy. OE-treated rats ate less than the controls, but additional effects on body composition on reduced diet were minimal. OE improved metabolic homoeostasis: better maintained glycaemia, lower cholesterol and shallower hormonal changes, but at the expense of slightly increased protein mobilisation. Conclusions: The data presented suggest that no advantages are accomplished by combining OE treatment and hypocaloric diets compared with OE alone, at least under the experimental conditions tested, since the effects were not additive. Despite OE affecting food intake, mechanisms other than that are deemed responsible for the mobilisation of body fat, since intake alone cannot explain the effects on body weight, nor the metabolic and hormonal changes in OE-treated rats. It is concluded that the combination of food restriction and OE may result in unwanted increased protein mobilisation with no synergy between both slimming treatments.

Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

“…OE effects on weight, energy, lipid, and protein were similar to the previously reported ones (4,9,21,22). Rimonabant effects and its rapid effect on appetite agree with previous studies (11).…”

“…OE has been found to produce in rats a synergic boosting of body fat loss both with a β 3 -adrenergic agent (21) and a serotoninergic drug, sibutramine (22), indicating that its mechanism of action was complementary of both thermogenesis and inhibition of appetite by enhancement of postsynaptic serotonin activity. Combination of OE and dietary restriction, however, showed no improvement over the administration of OE alone in the handling of body fat, but OE markedly improved the body metabolic and hormonal environment when compared with restricted diet alone (9).…”

“…The powerful lipolytic effect of OE occurs in parallel to a decrease in overall glucose utilization (6), maintenance of glycemia and liver glycogen (7), and decrease of circulating insulin (and insulin resistance) and leptin (6 -8). OE does not need the concurrence of dietary restrictions to induce the loss of body weight (9). Rimonabant (SR141716), an inhibitor of the CB1 cannabinoid receptor (10), has been found to markedly decrease appetite, both in rats (11) and humans (12).…”

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

“…All animal handling procedures were approved by the Animal Management Ethics Committee of the University of Barcelona and were in full compliance with the norms and directives of the EU, Spain and Catalonia. The rats were given the standard working OE dose: a single 10 nmol/g gavage of OE (OED, Barcelona, Spain) in 0.2 mL of sunflower oil [32]. The rats were then killed by decapitation, and the blood was recovered and allowed to clot.…”

Oleoyl-estrone affects lipid metabolism in adrenalectomized rats treated with corticosterone through modulation of SREBP1c expression

“…OE mobilization of lipid specially affects white adipose tissue (WAT), by decreasing its mass [2] through apoptosis [3] and massive loss of lipid [1,2], accompanied by a decrease in food intake and the maintenance of energy expenditure [4]. OE effects have been observed in a number of animals models, including genetic [5,6] or dietary [7,8] models of obesity, even using hyperlipidic diets [9]. In addition to the modification of energy balance, OE also decreases insulin resistance and markedly lowers cholesterol levels, improving hyperlipidemia [10].…”