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Marià Alemany - One of the best experts on this subject based on the ideXlab platform.
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In the rat, Estrone sulphate is the main serum metabolite of oral oleoyl-Estrone.
Journal of Endocrinological Investigation, 2007Co-Authors: C Cabot, J. A. Fernández-lópez, D. González-martínez, Marià AlemanyAbstract:Two different oral doses of oleoyl-Estrone: 1 and 10 nmol/g a day were given once to male Wistar rats. the serum levels of free Estrone, Estrone sulphate, estradiol, and acyl-Estrone were measured at intervals up to 72 h after the gavage. Oleoyl-Estrone was rapidly absorbed; with the 1 nmol/g dose no changes were observed in plasma acyl-Estrone but levels increased dramatically with 10 nmol/g, peaking at 6 h; high acyl-Estrone levels were maintained up to 24 h, returning to normalcy at 48 h. With the 10 nmol/g dose, free Estrone at most doubled its levels but Estrone sulphate concentrations rose by one order of magnitude; in both cases, the increases soon (2 h) reached a plateau that was maintained for almost two days. Estradiol levels remained unchanged except for a transient peak at 2 h at the 10 nmol/g dose. The relationship between free Estrone and its sulphate was linear, and those of Estrone and Estrone sulphate versus acyl-Estrone showed the existence of an upper serum concentration limit for both molecules. The results hint at Estrone sulphate being an important metabolite of oleoyl-Estrone disposal, confirm the limited estrogenic response to oleoyl-Estrone administration and agree with a rapid absorption and disposal of oleoyl-Estrone, nevertheless maintaining high circulating levels of the ester for a time after its oral administration.
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effects of oleoyl Estrone with dexfenfluramine sibutramine or phentermine on overweight rats
European Journal of Pharmacology, 2005Co-Authors: Raquel Ferrerlorente, C Cabot, Jose Antonio Fernandezlopez, Xavier Remesar, Marià AlemanyAbstract:We studied the combination of oleoyl-Estrone with either dexfenfluramine, sibutramine or phentermine in overweight male rats treated for 10 days in order to determine whether they shared a mechanism of action. Oleoyl-Estrone, dexfenfluramine and sibutramine decreased body weight and energy (essentially lipids); losses were higher when combined with oleoyl-Estrone. Glycemia was maintained except under phentermine; oleoyl-Estrone induced decreases in triacylglycerols, cholesterol, insulin and HOMA (homeostasis model assessment). Combination of oleoyl-Estrone and sibutramine resulted in the loss of up to 29% body energy in 10 days. Energy expenditure was maintained. The effects of oleoyl-Estrone and dexfenfluramine or sibutramine on appetite were substantially additive. All oleoyl-Estrone-treated rats showed increased insulin sensitivity. In conclusion, combined treatment of overweight rats with oleoyl-Estrone and sibutramine or dexfenfluramine results in a dramatic loss of weight and fat, whilst maintaining circulating energy homoeostasis.
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Effects of oral Estrone on rat energy balance.
Steroids, 2005Co-Authors: Raquel Ferrer-lorente, Xavier Remesar, J. A. Fernández-lópez, Beatriz García-peláez, Susana Gómez-ollés, Marià AlemanyAbstract:Abstract Oral doses of Estrone from 10 nmol/(kg day) to 10 μmol/(kg day) were given to adult Wistar male rats for 10 days. Body composition, energy balance, total body Estrone balance and plasma metabolites and hormones were measured at the end of the treatment. Body weight (as well as food intake, body energy, fat and water accrual) increased at doses in the 10–100 nmol/(kg day) range, but decreased at higher doses. Energy expenditure decreased with increasing doses of Estrone. Plasma metabolite changes suggested the maintenance of energy homeostasis, and lipid parameters indicated that lipid mobilization increased with the increasing doses of Estrone. Plasma Estrone, acyl-Estrone and estradiol levels decreased at low doses and increased at high doses of Estrone. We conclude that: (a) repeated Estrone gavages, even at very high doses, do not result in the accrual of Estrone in the body; (b) low doses of Estrone promote growth and high doses decrease body mass and fat accretion; (c) administration of Estrone at low doses decreases its circulating levels and the levels of estradiol and acyl-Estrone, a situation reverted at higher doses and (d) Estrone administration induces a dose-dependent shift towards lower energy expenditure.
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Zucker obese rats store less acyl-Estrone than lean controls
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M M Grasa, J López-martí, M Díaz-silva, Marià AlemanyAbstract: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 μmol/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.
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Zucker obese rats store less acyl-Estrone than lean controls.
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M Díaz-silva, J. López‐martí, Marià AlemanyAbstract: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 μmol/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.
Shuo Wang - One of the best experts on this subject based on the ideXlab platform.
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separation and determination of Estrone in environmental and drinking water using molecularly imprinted solid phase extraction coupled with hplc
IEEE Journal of Solid-state Circuits, 2008Co-Authors: Shuo Wang, Guozhen Fang, Yan ZhangAbstract:Estrone has been identified as an important potential endocrine-disrupting compound, so that sensitive and reliable analytical methods are required for its determination and the assurance of human health. Using Estrone as the template, acrylamide as the functional monomer, and methacryloxypropyltrimethoxysilane as the cross-linker, an organic-inorganic hybrid material has been synthesized by the molecular imprinting technique combined with a non-hydrolytic so-gel process. The synthesized polymer was characterized by FT-IR and static adsorption experiments, and the results showed that it had good recognition and selective ability for Estrone. A novel method for separation and determination of trace Estrone in water samples was developed using molecularly imprinted solid phase extraction coupled with HPLC. Under the selected experimental condition, the detection limit (S/N = 3) was 9.3 ng/L, and the RSD for five replicate extractions of 10 μg/L Estrone was less than 5.0%. This method was employed for quantitative determination of Estrone in river, lake, and tap water with recoveries ranging from 83.38 to 98.12%.
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development of a solid phase extraction enzyme linked immunosorbent assay method for the determination of Estrone in water
Analytica Chimica Acta, 2004Co-Authors: Shuo Wang, Alice N Lee, Robin D Allan, Ivan R KennedyAbstract:Estrone has been identified as a potential endocrine-disrupting chemical (EDC). To facilitate its analysis, a highly selective and sensitive enzyme-linked immunosorbent assay (ELISA) method with a simple solid-phase extraction (SPE) for analysis of Estrone in aquatic environments has been developed. The specific polyclonal antibody was produced against a conjugate of Estrone-3-hemisuccinate and keyhole limpet hemocyanin (KLH). The obtained ELISA showed specific recognition of Estrone, without cross-reactions for three other major estrogenic compounds (17β-estradiol, estriol, and 17α-ethynylestradiol) commonly found in water. The ELISA had a limit of detection of 0.14 μg/l Estrone in water. Combining a SPE method to extract and pre-concentrate Estrone from water samples and ELISA to specifically quantify Estrone content, the SPE-ELISA can detect Estrone down to 1.25 ng/l level in water. Good recovery with spiked river water was obtained with this SPE-ELISA method. The developed SPE-ELISA system was applied to analyze the real influent and effluent samples of sewage treatment plant in Penrith (Australia) and the results correlated well with those obtained using GC and HPLC methods. The developed SPE-ELISA method is capable of being applied for the specific detection and routine monitoring of Estrone in environmental water samples.
Xavier Remesar - One of the best experts on this subject based on the ideXlab platform.
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effects of oleoyl Estrone with dexfenfluramine sibutramine or phentermine on overweight rats
European Journal of Pharmacology, 2005Co-Authors: Raquel Ferrerlorente, C Cabot, Jose Antonio Fernandezlopez, Xavier Remesar, Marià AlemanyAbstract:We studied the combination of oleoyl-Estrone with either dexfenfluramine, sibutramine or phentermine in overweight male rats treated for 10 days in order to determine whether they shared a mechanism of action. Oleoyl-Estrone, dexfenfluramine and sibutramine decreased body weight and energy (essentially lipids); losses were higher when combined with oleoyl-Estrone. Glycemia was maintained except under phentermine; oleoyl-Estrone induced decreases in triacylglycerols, cholesterol, insulin and HOMA (homeostasis model assessment). Combination of oleoyl-Estrone and sibutramine resulted in the loss of up to 29% body energy in 10 days. Energy expenditure was maintained. The effects of oleoyl-Estrone and dexfenfluramine or sibutramine on appetite were substantially additive. All oleoyl-Estrone-treated rats showed increased insulin sensitivity. In conclusion, combined treatment of overweight rats with oleoyl-Estrone and sibutramine or dexfenfluramine results in a dramatic loss of weight and fat, whilst maintaining circulating energy homoeostasis.
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Effects of oral Estrone on rat energy balance.
Steroids, 2005Co-Authors: Raquel Ferrer-lorente, Xavier Remesar, J. A. Fernández-lópez, Beatriz García-peláez, Susana Gómez-ollés, Marià AlemanyAbstract:Abstract Oral doses of Estrone from 10 nmol/(kg day) to 10 μmol/(kg day) were given to adult Wistar male rats for 10 days. Body composition, energy balance, total body Estrone balance and plasma metabolites and hormones were measured at the end of the treatment. Body weight (as well as food intake, body energy, fat and water accrual) increased at doses in the 10–100 nmol/(kg day) range, but decreased at higher doses. Energy expenditure decreased with increasing doses of Estrone. Plasma metabolite changes suggested the maintenance of energy homeostasis, and lipid parameters indicated that lipid mobilization increased with the increasing doses of Estrone. Plasma Estrone, acyl-Estrone and estradiol levels decreased at low doses and increased at high doses of Estrone. We conclude that: (a) repeated Estrone gavages, even at very high doses, do not result in the accrual of Estrone in the body; (b) low doses of Estrone promote growth and high doses decrease body mass and fat accretion; (c) administration of Estrone at low doses decreases its circulating levels and the levels of estradiol and acyl-Estrone, a situation reverted at higher doses and (d) Estrone administration induces a dose-dependent shift towards lower energy expenditure.
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Zucker obese rats store less acyl-Estrone than lean controls
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M M Grasa, J López-martí, M Díaz-silva, Marià AlemanyAbstract: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 μmol/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.
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Zucker obese rats store less acyl-Estrone than lean controls.
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M Díaz-silva, J. López‐martí, Marià AlemanyAbstract: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 μmol/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.
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Intestinal handling of an oral oleoyl-Estrone gavage by the rat
Life Sciences, 2001Co-Authors: Montserrat Esteve, Xavier Remesar, J. A. Fernández-lópez, Paulina Savall, Maria Teresa Blay, Marià AlemanyAbstract:Abstract Adult Zucker lean (Fa/?) female rats received a single 250 nmol oral gavage of 3 H-labelled oleoyl-Estrone in 0.2 ml of sunflower oil. After one hour, samples of arterial, portal and suprahepatic blood, and lymph were obtained and fractioned to determine the amount of radioactivity present in the form of free Estrone, acyl-Estrone and hydrophilic Estrone esters in the blood of each vessel. Lipoprotein fractions (chylomicra + VLDL, LDL, HDL and lipoprotein-depleted plasma) were also analysed as well as the distribution of absorbed 3 H-Estrone in the intestine, specific organs and carcass. About one third of the oleoyl-Estrone dose recovered was found in the tissues, mainly in the blood, the rest remaining relatively untouched in the intestinal content. High hypothalamic Estrone uptake (compared with the rest of the brain) was observed. Data from non-radioactive Estrone measurements showed a similar pattern of absorption and tissue distribution to that obtained by 3 H-Estrone tracking alone. In both cases, most of the Estrone present in the intestinal lumen was absorbed as intact oleoyl-Estrone, but a significant part was absorbed as free Estrone. There is a net transfer of 3 H-Estrone into portal blood HDL, and part of the 3 H-Estrone is also loaded into lymph-carried chylomicra. A large share of free Estrone is filtered by the liver, but most of the acyl-Estrone absorbed passes unaltered. The oral administration of oleoyl-Estrone results in significant absorption of the unaltered molecule, which is transferred to lymph-carried chylomicra and also directly to plasma HDLs. It may be inferred that the HDL fraction contains the physiological carrier of oleoyl-Estrone in its role of ponderostat signal.
J. A. Fernández-lópez - One of the best experts on this subject based on the ideXlab platform.
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In the rat, Estrone sulphate is the main serum metabolite of oral oleoyl-Estrone.
Journal of Endocrinological Investigation, 2007Co-Authors: C Cabot, J. A. Fernández-lópez, D. González-martínez, Marià AlemanyAbstract:Two different oral doses of oleoyl-Estrone: 1 and 10 nmol/g a day were given once to male Wistar rats. the serum levels of free Estrone, Estrone sulphate, estradiol, and acyl-Estrone were measured at intervals up to 72 h after the gavage. Oleoyl-Estrone was rapidly absorbed; with the 1 nmol/g dose no changes were observed in plasma acyl-Estrone but levels increased dramatically with 10 nmol/g, peaking at 6 h; high acyl-Estrone levels were maintained up to 24 h, returning to normalcy at 48 h. With the 10 nmol/g dose, free Estrone at most doubled its levels but Estrone sulphate concentrations rose by one order of magnitude; in both cases, the increases soon (2 h) reached a plateau that was maintained for almost two days. Estradiol levels remained unchanged except for a transient peak at 2 h at the 10 nmol/g dose. The relationship between free Estrone and its sulphate was linear, and those of Estrone and Estrone sulphate versus acyl-Estrone showed the existence of an upper serum concentration limit for both molecules. The results hint at Estrone sulphate being an important metabolite of oleoyl-Estrone disposal, confirm the limited estrogenic response to oleoyl-Estrone administration and agree with a rapid absorption and disposal of oleoyl-Estrone, nevertheless maintaining high circulating levels of the ester for a time after its oral administration.
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Effects of oral Estrone on rat energy balance.
Steroids, 2005Co-Authors: Raquel Ferrer-lorente, Xavier Remesar, J. A. Fernández-lópez, Beatriz García-peláez, Susana Gómez-ollés, Marià AlemanyAbstract:Abstract Oral doses of Estrone from 10 nmol/(kg day) to 10 μmol/(kg day) were given to adult Wistar male rats for 10 days. Body composition, energy balance, total body Estrone balance and plasma metabolites and hormones were measured at the end of the treatment. Body weight (as well as food intake, body energy, fat and water accrual) increased at doses in the 10–100 nmol/(kg day) range, but decreased at higher doses. Energy expenditure decreased with increasing doses of Estrone. Plasma metabolite changes suggested the maintenance of energy homeostasis, and lipid parameters indicated that lipid mobilization increased with the increasing doses of Estrone. Plasma Estrone, acyl-Estrone and estradiol levels decreased at low doses and increased at high doses of Estrone. We conclude that: (a) repeated Estrone gavages, even at very high doses, do not result in the accrual of Estrone in the body; (b) low doses of Estrone promote growth and high doses decrease body mass and fat accretion; (c) administration of Estrone at low doses decreases its circulating levels and the levels of estradiol and acyl-Estrone, a situation reverted at higher doses and (d) Estrone administration induces a dose-dependent shift towards lower energy expenditure.
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Zucker obese rats store less acyl-Estrone than lean controls
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M M Grasa, J López-martí, M Díaz-silva, Marià AlemanyAbstract: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 μmol/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.
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Zucker obese rats store less acyl-Estrone than lean controls.
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M Díaz-silva, J. López‐martí, Marià AlemanyAbstract: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 μmol/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.
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Intestinal handling of an oral oleoyl-Estrone gavage by the rat
Life Sciences, 2001Co-Authors: Montserrat Esteve, Xavier Remesar, J. A. Fernández-lópez, Paulina Savall, Maria Teresa Blay, Marià AlemanyAbstract:Abstract Adult Zucker lean (Fa/?) female rats received a single 250 nmol oral gavage of 3 H-labelled oleoyl-Estrone in 0.2 ml of sunflower oil. After one hour, samples of arterial, portal and suprahepatic blood, and lymph were obtained and fractioned to determine the amount of radioactivity present in the form of free Estrone, acyl-Estrone and hydrophilic Estrone esters in the blood of each vessel. Lipoprotein fractions (chylomicra + VLDL, LDL, HDL and lipoprotein-depleted plasma) were also analysed as well as the distribution of absorbed 3 H-Estrone in the intestine, specific organs and carcass. About one third of the oleoyl-Estrone dose recovered was found in the tissues, mainly in the blood, the rest remaining relatively untouched in the intestinal content. High hypothalamic Estrone uptake (compared with the rest of the brain) was observed. Data from non-radioactive Estrone measurements showed a similar pattern of absorption and tissue distribution to that obtained by 3 H-Estrone tracking alone. In both cases, most of the Estrone present in the intestinal lumen was absorbed as intact oleoyl-Estrone, but a significant part was absorbed as free Estrone. There is a net transfer of 3 H-Estrone into portal blood HDL, and part of the 3 H-Estrone is also loaded into lymph-carried chylomicra. A large share of free Estrone is filtered by the liver, but most of the acyl-Estrone absorbed passes unaltered. The oral administration of oleoyl-Estrone results in significant absorption of the unaltered molecule, which is transferred to lymph-carried chylomicra and also directly to plasma HDLs. It may be inferred that the HDL fraction contains the physiological carrier of oleoyl-Estrone in its role of ponderostat signal.
R M Massanés - One of the best experts on this subject based on the ideXlab platform.
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Zucker obese rats store less acyl-Estrone than lean controls
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M M Grasa, J López-martí, M Díaz-silva, Marià AlemanyAbstract: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 μmol/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.
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Zucker obese rats store less acyl-Estrone than lean controls.
International Journal of Obesity, 2003Co-Authors: R M Massanés, Xavier Remesar, J. A. Fernández-lópez, M Díaz-silva, J. López‐martí, Marià AlemanyAbstract: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 μmol/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.