Oleoyl-estrone induces the massive loss of body weight in Zucker fa/fa rats fed a high-energy hyperlipidic diet

López-Martí, J; Díaz-Silva, M; Salas, Anna Santos; Grasa, María del Mar; Fernández-López, José Antonio; Remesar, Xavier; Alemany, M

doi:10.1016/s0955-2863(00)00106-6

Cited by 14 publications

(26 citation statements)

References 26 publications

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“…OE inhibits leptin synthesis and decreases its levels (7). The mechanism for this action is unclear, but in the case of OE, it seems to go beyond the decrease in WAT mass that obviously reduces the main site of leptin production (39). The additive effects of rimonabant and OE are not directly related to the mass of adipose tissue and are probably the cause of different regulation paths acting on the secretion of leptin.…”

Section: Discussionmentioning

confidence: 99%

Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

2007

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Abstract. Oleoyl-estrone (OE) decreases appetite, maintains energy expediture, induces lipolysis (sparing protein), and decreases cholesterolemia and insulin resistance. Rimonabant (SR141716) is a cannabinoid-receptor inhibitor that decreases appetite and mobilizes fat. We studied whether their combination improves their slimming effects. Male overweight rats received daily gavages of 5.3 mg / kg OE, 10 mg/ kg rimonabant, or both drugs during 10 days. Body weight and composition, energy balance, adipose tissue weight, and serum hormones and metabolites were measured. OE halved food intake and maintained energy expenditure at the expense of body fat. Rimonabant effects on appetite and energy balance were less marked, resulting in lower lipid mobilization. OE and rimonabant followed the OE pattern, with no additive or synergic effects. Glycemia was maintained, but OE decreased insulin, GLP-1, and cholesterol, whilst rimonabant increased cholecystokinin and cholesterol, and decreased NEFA. Both drugs decreased leptin and triacylglycerols; ghrelin was unchanged. The results hint at different mechanisms of action of both drugs: we can assume that OE effects do not involve the cannabinoid pathway. OE does not seem to act, either, after 10 days, through the secretion of ghrelin or the intestinal appetite-controlling peptides tested.

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Section: Discussionmentioning

confidence: 99%

Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

2007

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“…11,26 Under OE, glucose levels are maintained in spite of a marked decrease of insulin. 10,11,17 In food deprivation or restriction, glycaemia is maintained at the expense of 3C fragments, essentially derived from amino acids through the glucose-alanine cycle. 27 However, under OE treatment there is no need for an enhanced liver glucose output, since peripheral utilisation of glucose is decreased, 28 which results in the sparing of protein.…”

Section: Discussionmentioning

confidence: 99%

“…A fattening protocol previously published 20 was used; the animals were fed for 5 weeks with a modified cafeteria diet 11,17 (fattening period). Afterwards, they were transferred to wire mesh-bottomed cages and were maintained for 5 days exclusively on a pellet ('maintenance' type, from Panlab, Barcelona, Spain) ad libitum diet (stabilisation period).…”

Section: Methodsmentioning

confidence: 99%

“…hunger pangs, hypoglycaemia), to enhance energy expenditure to speed up the process of fat disposal, or to maintain the weight loss during and after treatment. 16 OE has been used, so far without association to limited food intake, both in rodents and humans, [17][18][19] since OE limits food intake by itself, and prevents the fall in energy expenditure 5,11 that accompanies food deprivation. 4 In the present study, we have explored the combined effects of severely limited food intake and OE treatment, in order to determine whether hypocaloric diets enhance the slimming effects of OE on mature overweight male rats.…”

Section: Introductionmentioning

confidence: 99%

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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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“…The energy gap is closed by the mobilisation of white adipose tissue (WAT) reserves [4], sparing body protein [3]. OE also decreases the high insulin [5] and hyperlipidemia of obese rats [6], particularly of cholesterol [6,7].…”

Section: Oleoyl-estrone Nature and Effectsmentioning

confidence: 99%

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

Vila

Cabot

Villarreal

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

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Oleoyl-estrone (OE) is a powerful anti-obesity compound that decreases food intake, decreases insulin resistance and circulating cholesterol. OE stimulates a severe loss of body fat by decreasing adipose tissue lipid synthesis and maintaining lipolysis. Therefore, the body economy loses lipid energy because energy expenditure is maintained. This study analyses the discrepancy between OE effects and the distribution of labelled OE in plasma. Estrone radioimmunoassay of organic solvent plasma extracts of rats treated with OE showed the massive presence of acyl-estrone, but saponification did not release estrone, but containing similar unknown compound. Analysis of label distribution in plasma after oral gavages of (3)H-OE showed the presence of a more hydrophilic compound than OE or any estrogen as well as (3)H(2)O, formed from (3)H-OE in the acidic stomach medium. OE was not attached to a specific transporter in plasma. Through serum HPLC analysis we found W, a labelled derivative more hydrophilic than OE or estrone. The results were confirmed using (14)C-OE. HPLC-MS/MS studies showed that plasma OE levels were one order of magnitude lower than those of W. When liver cell cytosols from rats laden with (3)H-OE were incubated with nuclei from untreated rats, the OE-derived label (i.e., Ws) was found attached to nuclear DNA. Neither estradiol nor estrone interfered with its binding. W is a fairly hydrophilic compound of low molecular weight containing the estrone nucleus, but it is not an ester because saponification or esterases do not yield estrone as OE does. It is concluded that OE acts through its conversion to W, its active form; which binds to a nuclear receptor different from that of estrogen. The estimated W serum levels are proportional to the pharmacological OE effects in vivo. We postulate W as a new type of hormone that exerts the full range of in vivo effects thus far attributed to OE. The full identification of W is anticipated to open the way for the development of new OE-like anti-obesity drugs.

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Oleoyl-estrone induces the massive loss of body weight in Zucker fa/fa rats fed a high-energy hyperlipidic diet

Cited by 14 publications

References 26 publications

Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

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

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

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