Rats Receiving the Slimming Agent Oleoyl-Estrone in Liposomes (Merlin-2) Decrease Food Intake but Maintain Thermogenesis

Sanchı́s, Daniel; F, Balada; Picó, Catalina; Grasa, Mar; Virgili, J.; Farrerons, C; Palou, Andreu; Fernández-López, José Antonio; Remesar, Xavier; Alemany, M.

doi:10.1076/apab.105.7.663.11391

Cited by 46 publications

(43 citation statements)

References 13 publications

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“…The main effect of oleoyl-estrone on plasma cholesterol, thus, can be traced to the increased turnover and shrinking pool of esterified cholesterol, another indication of accelerated lipoprotein handling parallel to white adipose tissue wasting and active lipid oxidation. 4,7 Insulin resistance alters the handling of lipoproteins, and thus that of HDL-cholesterol. 16,17 Hyperinsulinaemia also increases the synthesis and decreases the absorption of cholesterol.…”

Section: Discussionmentioning

confidence: 99%

“…This active utilisation of lipid reserves is carried out essentially by decreasing the lipid stores in white adipose tissue, 1 and the increased muscle utilisation of lipids 3 that result in a marked decrease of the respiratory quotient, 1 sparing body protein in a context in which food intake was decreased and energy expenditure maintained. 4 Chronic oleoyl-estrone treatment also induces a decrease in insulin levels and insulin resistance, with maintenance of plasma glucose and liver glycogen. 5,6 The imbalance between maintained energy expenditure and decreased energy intake induced by oleoyl-estrone treatment is maintained at the expense of lipid stores; 2 the massive mobilisation of adipose tissue lipid, and its oxidation, 1,7 spares glucose and protein, 4 increasing the transport of lipids by the blood.…”

Section: Introductionmentioning

confidence: 99%

“…4 Chronic oleoyl-estrone treatment also induces a decrease in insulin levels and insulin resistance, with maintenance of plasma glucose and liver glycogen. 5,6 The imbalance between maintained energy expenditure and decreased energy intake induced by oleoyl-estrone treatment is maintained at the expense of lipid stores; 2 the massive mobilisation of adipose tissue lipid, and its oxidation, 1,7 spares glucose and protein, 4 increasing the transport of lipids by the blood.…”

Section: Introductionmentioning

confidence: 99%

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Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

et al. 2005

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OBJECTIVE: Oral treatment with oleoyl-estrone induces the loss of body fat and improvement of insulin resistance. Since cholesterol levels are deeply affected by oleoyl-estrone, we investigated here whether short-term treatment affected cholesterol turnover and overall metabolite changes. DESIGN: Wistar female rats received a single oral dose of 10 mmol/kg oleoyl-estrone in 0.2 ml of sunflower oil. Groups of animals were killed at timed intervals and blood samples were taken. In a second experiment series, rats had implanted carotid and jugular cannulas and were given a single gavage of oleoyl-estrone. These rats were used for the measurement of the cholesterol turnover rate. MEASUREMENTS: Body weight change and food intake: Glucose, total and HDL-cholesterol, triacylglycerols, 3-hydroxybutyrate, nonesterified fatty acids, insulin, HOMA score in the rats of the first series. Cholesterol: Cholesterol pool changes and cholesterol turnover rates in the rats of the second series. RESULTS: OE induced early effects, decreasing food intake, cholesterol and HDL-cholesterol levels, and increasing insulin sensitivity (HOMA score). OE also increased cholesteryl-ester turnover, and decreased circulating total cholesterol, especially esterified cholesterol pools. CONCLUSIONS: The role of early changes in insulin sensitivity induced by oral OE cannot explain per se the deep changes in cholesterol handling, essentially a consequence of accelerated lipoprotein turnover. However, the increase in cholesteryl-ester turnover observed with OE treatment may be, at least in part, a consequence of the decrease in insulin resistance. The compounded effect of increased insulin sensitivity and accelerated lipoprotein turnover may help explain the early and marked hypocholesterolaemic effects of OE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

et al. 2005

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“…6 The oral administration of OE to lean, genetically obese or dietary-obese rodents induces a marked loss of body fat, 7,8 primarily due to a decrease in voluntary food intake coupled with the maintenance of energy expenditure. 9 Glucose levels are maintained in spite of marked decreases in insulin and leptin, 10 a consequence of OE-elicited increase in insulin sensitivity/decrease in insulin resistance, 11 which results in the maintenance of liver glycogen stores regardless of the severe drainage of body energy. 10 Lipid mobilisation, however, does not massively increase circulating lipids, since lipid oxidation is also increased as shown by the lowering of the respiratory quotient, 5 and marked decrease in cholesterol levels 12 coupled with enhanced muscle lipoprotein lipase activity.…”

Section: Introductionmentioning

confidence: 99%

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

2006

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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.

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“…6,16 On the other hand, the overall loss of fat and decreased energy intake clearly indicates that oleoyl-estrone-treated rats oxidize significant amounts of fat from their WAT stores; respiratory quotient measurements agree with this interpretation. 5,17 However, neither the site of this oxidation nor the mechanism of lipid transport are known.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2002

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OBJECTIVE:To study the effect of oral oleoyl-estrone on the plasma lipoprotein profile and tissue lipase activities in order to determine the handling of circulating lipids by adipose tissue, liver and muscle of obese female rats. DESIGN: Lean (Fa=?) and obese (fa=fa) female Zucker rats treated for 10 days with a daily gavage of 0.2 ml sunflower oil containing 0 (controls) or 10 mmol=kg of oleoyl-estrone. After sacrifice, samples of tissues and plasma were taken. MEASUREMENTS: Plasma lipoprotein classes and composition; lipoprotein lipase and hepatic lipase activities in plasma, liver, skeletal muscle and periovaric and mesenteric white adipose tissue (WAT). RESULTS: Oleoyl-estrone decreased plasma cholesterol (mainly in HDLs: 76%) of lean rats, but dramatically decreased all lipid classes in obese rats, in which chylomicra and VLDL lost most of their triacylglycerols (95 and 81%, respectively). Hepatic lipase activity decreased markedly with oleoyl-estrone in all groups, both in plasma (79% lean, 100% obese) and liver (62% in both groups). Lipoprotein lipase activity was largely unchanged by oleoyl-estrone in lean rats, but in the obese it decreased in WAT (82% in periovaric, and 49% in mesenteric), and increased in plasma (Â4) and in skeletal muscle (Â5); liver levels showed no change. CONCLUSIONS: The shift observed in obese rats from a decrease in liver and WAT lipoprotein lipase and hepatic lipase activities to an increase in muscle lipoprotein lipase is coincident with the hypolipemic effect of oleoyl-estrone, especially in obese rats, and indicates that muscle is a key site for the disposal of endogenous fat mobilized due to oleoyl-estrone treatment.

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Rats Receiving the Slimming Agent Oleoyl-Estrone in Liposomes (Merlin-2) Decrease Food Intake but Maintain Thermogenesis

Cited by 46 publications

References 13 publications

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

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

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

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