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Biomedical subjects

M M Grasa

Publications and source records attributed to M M Grasa.

At least 19 recordsLinked to original sources
PubMed2002

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

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 micromol/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 (x4) and in skeletal muscle (x5); 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.

Adipose Tissue↗
PubMed2002

Effect of oral oleoyl-estrone on adipose tissue composition in male rats.

OBJECTIVE: To determine whether the oral administration of oleoyl-estrone has similar mass-decreasing effects on the main different sites of white adipose tissue (WAT). DESIGN: Adult male Zucker lean rats were given a daily oral gavage of oleoyl-estrone (OE, 10 micromol/kg) in 0.2 ml of sunflower oil for 10 days, and were compared with controls receiving only the oil. The mass of the main WAT sites: subcutaneous, epididymal, mesenteric, retroperitoneal, gluteal, perirenal and interscapular, as well as perirenal and interscapular brown adipose tissue (BAT), were dissected and studied. MEASUREMENTS: The tissue weight, DNA, protein, lipid and total cholesterol content, together with the levels of leptin and acyl-estrone in the larger WAT and BAT masses, were measured. RESULTS: The weights of WAT depots were correlated with body weight but those of BAT were not. Cell size was maximal for epididymal and mesenteric and minimal for subcutaneous and retroperitoneal WAT and BAT. Differences were detected in DNA, and in protein and lipid content between distinct WAT sites. OE treatment tended to decrease cell number and cell size in WAT; only small differences in composition were found between WAT locations inside the visceral cavity and those outside. Decreases in lipid content were maximal in mesenteric fat. Leptin and acyl-estrone content were fairly uniform at the different WAT sites, except for high concentrations in gluteal WAT. OE induced a greater decrease in leptin and acyl-estrone than in DNA and lipids; changes in these hormones were fairly parallel in all sites. CONCLUSIONS: In general, the differences in composition between visceral and peripheral subcutaneous WAT and their responses to OE were less marked than the individual differences observed between specific sites, regardless of location. WAT sites are fairly diverse in composition, but their response to OE treatment was uniform. OE decreased the weight of WAT through reduction of both cell numbers and size; but did not change the mass or composition of BAT significantly. The effects of OE are more marked in the hormonal signals (leptin and acyl-estrone) from the tissue than in its composition and mass.

Adipose Tissue↗
PubMed2001

Oleoyl-estrone does not have direct estrogenic effects on rats.

The estrogenic effects of oleoyl-estrone (OE) administration, either though continuous i.v. infusion with osmotic minipumps or administered by daily oral gavage, were studied. Binding of OE to human recombinant purified alpha receptors was negligible, and that of estrone (E1) was only a fraction of 17beta-estradiol (E2) binding. Intravenous--but not oral--OE administration resulted in marked increases of both E1 and E2 in rat plasma, but oral OE did not induce significant changes in either plasma hormone in Wistar or Zucker rats. The weight of uteri and ovaries increased with time of administration in Zucker rats treated with i.v. OE, but inguinal mammary gland proliferation between subcutaneous adipose tissue was even more marked. Oral administration of OE, however, did not increase either uterine weight or mammary gland proliferation, even at doses (10 micromol/kg x d) higher than those given i.v. (3.5 micromol/kg x d). The results indicate that i.v. administration of OE resulted in limited estrogenic effects mainly due to the high accumulation of E1 giving rise to significant increases in E2. On the other hand, oral administration of OE, even at higher daily doses, did not increase the circulating levels of either estrogen and, therefore, there were no significant effects on mammary gland proliferation or uterine weight. The oral administration of OE as a slimming drug, then, do not result in estrogenic side effects over a wide range of daily doses.

Adipose Tissue↗
PubMed2001

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

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.

Administration, Oral↗
PubMed2001

Modulation of corticosterone availability to white adipose tissue of lean and obese Zucker rats by corticosteroid-binding globulin.

Corticosterone-binding (CB) capacity was determined in periovarian and subcutaneous white adipose tissue (WAT), as well as in plasma of lean and obese Zucker rats. In lean rats, plasma CB was twice the level of obese rats. In lean rat WAT, dexamethasone binding accounted for only 0.05-0.09% of corticosterone binding, and aldosterone bound even less; in the obese rats, dexamethasone accounted for 0.2 - 0.3 % of corticosterone binding. Scatchard plots showed that KD for corticosterone was 3.1 nM (WAT) or 3.4 nM (plasma) in lean rats and 1.8 nM (WAT) or 1.5 nM (plasma) in obese rats. The total CB capacity in WAT was lower in the obese than in lean rats (47-50%). Plasma non-esterified fatty acid levels were higher in obese rats. The results suggest that CBG may limit the access of glucocorticoids to adipocytes more weakly in obese rats because of the lower CBG. Fatty acids may increase the affinity of CBG for corticosterone, which would make WAT cells less accessible to circulating glucocorticoids. The modulation of CBG by fatty acids may protect fat reserves by decreasing the sensitivity of WAT to glucocorticoids.

Adipose Tissue↗
PubMed2000

Oral oleoyl-estrone induces the rapid loss of body fat in Zucker lean rats fed a hyperlipidic diet.

OBJECTIVE: To test whether oleoyl-estrone affects body weight when given orally, which may help curtail the secondary growth-boosting effects of derived estrone. DESIGN: The rats were fed for 15 days with a powdered hyperlipidic diet (16.97 MJ/kg metabolizable energy) in which 46.6% was lipid-derived and 16.1% protein-derived energy (HL group), containing 1.23+/-0.39micromol/kg of fatty-acyl esters of estrone. This diet was supplemented with additional oleoyl-estrone to produce diets with 2.5 micromol/kg (diet OE2.5), 4.4 micromol/kg (diet OE4.4), and 33.3 micromol/kg content in fatty-acyl estrone (diet OE33). SUBJECTS: Twelve-week old female Zucker lean (Fa/?) rats initially weighing 200-235g. MEASUREMENTS: Food intake and body weight changes; urine and droppings production and nitrogen content. Body composition (water, lipid, protein) and total energy. Energy and nitrogen balances. Plasma chemistry including free amino acids. RESULTS: Oral administration of oleoyl-estrone in a hyperlipidic diet resulted in significant losses of fat, energy and, ultimately, weight, which were dependent on the dose of oleoyl-estrone ingested. Treatment induced the maintenance of energy expenditure combined with lower food intake, creating an energy gap that was filled with internal fat stores whilst preserving body protein. The decrease in food intake was not a consequence of food aversion but of diminished appetite. Energy expenditure was practically constant for all groups except for the OE33, which showed values about 25% lower than the controls. In most of the groups studied, there was a net protein deposition in spite of severe lipid and energy drainage. Amino acid levels agreed with this N-sparing shift. In spite of lowered energy intake, the N balance was positive or near zero in all groups, with a sizeable N-gap in controls and in lower-dose groups that disappeared in the OE33 group. CONCLUSION: Treatment of rats with a hyperlipidic diet containing added oleoyl-estrone resulted in the dose-related loss of fat reserves with scant modification of other metabolic parameters and preservation of body protein. The results agree with the postulated role of oleoyl-estrone as a ponderostat signal and open the way for its development as anti-obesity drug.

Adipose Tissue↗
PubMed2000

Oleoyl-estrone lowers the body weight of both ob/ob and db/db mice.

Homozygous obese db/db (BKS-Lepr(db) and ob/ob (B6-Lep(ob)) mice were treated for 14 days with a continuous infusion of a fat emulsion (controls) or loaded with oleoyl-estrone at doses of 12.5 and 50 nmol/g x d using surgically inserted osmotic minipumps. Treatment with oleoyl-estrone resulted in a marked decrease in body weight in both strains, compared with the unchecked growth of controls. In db/db mice, plasma urea and insulin, as well as liver lipid decreased with treatment. In ob/ob mice, the effect on insulin was more marked, in parallel with higher plasma lipids pointing to increased fat mobilisation. The results suggest that oleoyl-estrone effects on body fat reserves and insulin resistance are not mediated by leptin, since ob/ob mice lack this hormone and in the db/db it is present but cannot induce effects because of defective leptin receptors; in both cases oleoyl-estrone treatment lowers body weight.

Animals↗
PubMed1999

Short-term treatment with estrone oleate in liposomes (Merlin-2) does not affect the expression of the ob gene in Zucker obese rats.

Young female Zucker fa/fa rats of 370-430 g were implanted with osmotic minipumps releasing 3.5 micromol/day-kg of estrone oleate in liposomes (Merlin-2) into the bloodstream for up to 14 days. Merlin-2 induced a sustained loss of appetite, and a decrease in body weight of 3.5%, which contrasts with the 8.2% increase in controls during the period studied. Plasma insulin, glucose and urea decreased, and liver glycogen increased with Merlin-2 treatment. Plasma ACTH and corticosterone increased to a maximum at the end of the experiment. The expression of the ob gene in adipose tissue was unchanged, and plasma leptin levels were also unchanged by treatment. Estrone levels increased more than 1500-fold, and estrone oleate rose 100-fold during treatment. The fact that estrone oleate had no effect on the leptin levels or expression in obese rats, in contrast with the marked inhibition observed in the lean suggests that the functionality of the leptin receptor is essential for estrone oleate inhibition of the ob gene. This also suggests that leptin may control ob gene expression in white adipose tissue and that estrone oleate may activate this process. The slimming effect of estrone oleate is, thus, not directly dependent on leptin, since both normoleptinemic and hyperleptinemic animals lose fat following treatment nor are the effects on appetite and energy expenditure mediated by leptin. However, leptin levels and the expression of the ob gene are directly linked with estrone oleate function. A possible involvement of leptin in estrone oleate action is postulated. The results support the participation of estrone oleate in the control of body weight and hint at the complexity of its regulation by leptin and glucocorticoids.

Animals↗
PubMed1999

Oleoyl-estrone treatment affects the ponderostat setting differently in lean and obese Zucker rats.

OBJECTIVE: To determine whether the slimming effects of treatment with oleoyl-estrone (OE) in liposomes of normal and obese rats are permanent, or disappear as soon as the treatment with the drug ceased. This study was devised to gain further knowledge on the postulated role of OE as a ponderostat signal, evaluating whether (in addition) it can lower the ponderostat setting of the rat. DESIGN: The rats were infused for 14d (using osmotic minipumps) with oleoyl-estrone in liposomes at a dose of 3.5 micromol/kg x d, and were studied up to one month after the treatment ceased. SUBJECTS: Young adult lean controls (CL) or treated (TL) and obese controls (CO) or treated (TO) Zucker rats. MEASUREMENTS: Energy balance, blood glucose, liver glycogen, plasma insulin, leptin corticosterone, ACTH and estrone (free and total) concentrations, and expression of the OB gene in white adipose tissue (WAT). RESULTS: The loss of body weight caused by OE was recovered quickly in the TO, which gained weight at the same rate as the CO. TL rats, however remained at the low weight attained for one month after the treatment ceased. However, no differences were observed in calculated energy expenditure (EE) between the TL and TC rats once treatment had stopped. In TL and TO rats, liver glycogen concentrations decreased to normal shortly after treatment ceased, and leptin expression and concentrations remained normal and unchanged after the end of OE treatment. In TO rats, plasma glucose, insulin and leptin were lower than in the CO. Total estrone concentrations decreased rapidly in TL rats and more slowly in the TO, and free estrone followed a similar pattern. CONCLUSION: Continuous infusion of liposomes loaded with OE resulted in a decreased energy intake (EI), maintenance of EE and the utilization of body fat reserves in lean and obese rats alike. This process ended in obese rats as soon as the infusion ceased, so that even when the levels of free and total estrone in plasma remained high, there was a marked (and relatively fast) shift toward the basal situation, which translated into an increase in EI, maintenance of estimated EE and a marked buildup of energy stores. In lean rats, the effects of OE on leptin concentrations and OB gene expression persisted after infusion ended.

Adrenocorticotropic Hormone↗
PubMed1999

Effect of food deprivation on rat plasma estrone fatty acid esters.

The present study was devised to determine whether the circulating levels of estrone fatty esters are modified by 6-48 h starvation in the rat, in parallel to changes in fat reserves, as a test to check the plausibility of its function as a ponderostat signal in the mammal. Food deprivation resulted in a decrease in glucose and triacylglycerols, rapid disappearance of liver glycogen and increases in fatty acids and, especially, 3-hydroxybutyrate. Insulin and leptin decreased, corticosterone and free estrone increased from 6 h onwards and total estrone levels were maintained. Starvation reduced the lipid content of the rat by 25.6%. Plasma esterified estrone levels decreased more slowly, by 13% in 48 h, but its circulating mass decreased in the same proportion as the total lipid content of the rat. The small change in circulating estrone fatty esters is consistent with the postulated role of oleoyl-estrone as a medium-term ponderostat signal.

3-Hydroxybutyric Acid↗
PubMed1998

Differential short-term distribution of estrone and oleoyl-estrone administered in liposomes to lean and obese Zucker rats.

Thirteen-week-old female Zucker lean (Fa/Fa) and obese (fa/fa) rats were injected through a cannula inserted in the left jugular vein with 1 mL/kg of 3H-labeled oleoyl-estrone in liposomes (Merlin-2) (i.e., 670 fmol, 84 kBq). The rats were killed 10 minutes later and dissected. The presence of intact or hydrolyzed oleoyl-estrone was later determined in all samples. The pattern of distribution of estrone was quite different from that of oleoyl-estrone both in rats that were lean and in those that were obese. Estrone was better retained by white adipose tissue than oleoyl-estrone. Liver, spleen, and lungs accumulated more oleoyl-estrone and split part of it, from 4.7% (lung, obese) to 27% (liver, lean). The overall high retention of estrone by the rat tissues results in its very low circulating levels. The fast splitting of liposome-carried oleoyl-estrone by most tissues (up to more than 67% by intestine and skin of lean rats) may help explain the rise in blood free estrone. The differences between lean and obese Zucker rats are mainly quantitative in the case of estrone, the main differences being found in blood and adipose tissues. However, when we compare the data for oleoyl-estrone, the differences cannot be dismissed simply as due to differences in body size or the extent of fat deposits. A large portion of the label remained in the blood of the rats that were obese but not in those that were lean, the tissues of which took up more label. Brown adipose tissue shows a fair affinity for oleoyl-estrone in the rats that were lean but practically does not retain label in the rats that were obese, suggesting that oleoyl-estrone may have a direct effect on brown adipose tissue. The decreased uptake of oleoyl-estrone in rats that were obese shows that the mechanism regulating the turnover or disposal of this signal is altered in this type of genetic obesity.

Adipose Tissue↗
PubMed1998

Oleoyl-estrone does not alter hypothalamic neuropeptide Y in Zucker lean and obese rats.

Female Zucker lean and obese rats were treated for 14 days with 3.5 micromol/kg oleoyl-estrone (OE) in liposomes (Merlin-2). After 0, 3, 6, 10, and 14 days of treatment, the rats were killed and hypothalamic nuclei (lateral preoptic, median preoptic, paraventricular, ventromedial and arcuate) were used for neuropeptide Y (NPY) radioimmunoassay. In 14 days, OE decreased food intake by 26% in lean and 38% in obese rats and energy expenditure by 6% in lean and 47% in obese rats; the body weight gap between controls and treated rats becoming -17.8% of initial b.wt. in the lean and -13.6% in the obese rats. Obese rats showed higher NPY levels in all the nuclei than the lean rats. Despite a negative energy balance and decreased food intake, there were practically no changes in NPY with OE treatment. The results indicate that oleoyl-estrone does not act through NPY in its control of either food intake or thermogenesis in lean and genetically obese rats.

Animals↗
PubMed1998

Effect of oleoyl-estrone administration on corticosterone binding to tissues of lean and obese Zucker rats.

A group of female Zucker lean and obese rats was treated with 3.5 micromol/day kg of oleoyl-estrone in liposomes (OE) injected i.v. continuously for 14 days with inserted osmotic minipumps. Samples of liver were extracted on days 0, 3, 6, 10 and 14 and the expression of corticosterone-binding globulin (CBG) was determined by Northern blot. On the same dates, the total binding capacity of plasma, liver, periovaric white adipose tissue (WAT) and subcutaneous WAT was also determined using tritium-labelled corticosterone. Treatment with OE resulted in diminished CBG gene expression in the liver, this being more marked in the obese rats. Basal (time 0) corticosterone binding was higher in the plasma, liver and WAT of lean rats. Treatment with OE resulted in a gradual and general loss of binding capacity in the plasma and all tissues studied, for lean and obese rats alike. Since CBG decreases may result in enhanced glucocorticoid availability (and effects), the global decrease in corticosterone binding observed can be interpreted as a counteractive response to the energy imbalance elicited by OE.

Adipose Tissue↗
PubMed1998

Effect of adrenalectomy on the slimming activity of liposome-carried oleoyl-estrone in the rat.

OBJECTIVE: To determine the extent of glucocorticoid counter-regulatory control in the slimming action of oleoylestrone. DESIGN: Control and adrenalectomized rats were subjected to a seven-day treatment with 3.5 micromol/kg/d oleoylestrone in liposomes injected i.v. continuously by implanted osmotic minipumps. SUBJECTS: Sham-operated control and adrenalectomized lean Zucker rats. MEASUREMENTS: Body weight and food intake; plasma glucose, urea, insulin, leptin and corticosterone; liver glycogen. RESULTS: Treatment with oleoyl-estrone resulted in decreases in body weight and in food intake, as well as in circulating glucose, insulin and leptin. Combined adrenalectomy and oleoyl-estrone treatment resulted in a loss of almost 15% body weight in only seven days, with a severe drop in circulating glucose and insulin, almost total disappearance of plasma leptin and liver glycogen and a 3-fold rise in circulating urea. Food intake decreased sharply, which resulted in the exhaustion of energy reserves. CONCLUSION: The results presented here, strongly support the hypothesis that glucocorticoids play an important role in the modulation of oleoyl-estrone-induced imbalance of energy intake and expenditure. The large effect of oleoyl-estrone on glucose, glycogen- and protein-derived (urea levels) energy in adrenalectomized rats, provides more evidence for the assumed protective role of glucocorticoids against the oleoyl-estrone-induced net loss of energy reserves. The results also show the powerful destabilizing effects of unchecked oleoyl-estrone on energy balance.

Adrenalectomy↗
PubMed1998

Corticosterone binding to tissues of adrenalectomized lean and obese Zucker rats.

The binding of corticosterone, dexamethasone and aldosterone was investigated in plasma and in homogenates of liver, kidney, brain, brown adipose tissue and visceral (periovaric) and subcutaneous white adipose tissues of Zucker lean and obese rats: intact controls, adrenalectomized and sham-operated. Corticosterone-binding globulin (CBG) accounted for most of the binding, whereas that of glucocorticoid and mineralocorticoid receptors was much lower. Plasma corticosterone levels increased in sham-operated and obviously decreased in the adrenalectomized animals. Sham-operated and adrenalectomized lean rats showed decreased plasma CBG; in the obese, CBG levels were lower than in controls and were not affected by either surgery. No variation with obesity or surgery was observed either in dexamethasone or aldosterone binding, the latter being practically zero in most samples. When expressed per unit of tissue protein, CBG activity was maximal in adipose tissues, with lowest values in brain and liver. In lean rats, tissue CBG activity decreased with either surgical treatment; no changes were observed in the obese, which also had lower CBG tissue levels. The relative lack of changes in CBG of obese rats suggests that they have lost -- at least in part -- the ability to counter-modulate the changes in glucocorticoid levels through CBG modulation, thus relying only on the control of corticosterone levels. This interpretation agrees with the postulated role of CBG modulating the availability of glucocorticoids to target cells.

Adipose Tissue↗
PubMed1997

Short-term handling of the slimming agent oleoyl-estrone in liposomes (Merlin-2) by the rat.

Female adult rats were injected in the jugular vein with oleoyl-3H-estrone incorporated into liposomes. The label rapidly disappeared from the blood, being taken up by the tissues, mainly liver, spleen and lung, which filtered most of the label. However, many other tissues, such as the heart, brown adipose tissue, adrenals and visceral fat incorporated significant amounts of oleoyl-estrone. The analysis of the form in which the label remained 10 min after the injection showed that it was hydrolysed in a large proportion even in liver and lungs. However, in most tissues (brain, brown and white - periovaric - adipose tissues and ovaries), intact oleoyl-estrone accounted for less than one quarter of all tissue label, and less than 10% in the case of subcutaneous adipose tissue and uterus. This rapid destruction of oleoyl-estrone is in agreement with the active role of this compound in the control of body weight.

Adipose Tissue↗
PubMed1997

Effect of the slimming agent oleoyl-estrone in liposomes on the body weight of Zucker obese rats.

OBJECTIVE: To determine whether the mechanisms by which estrone acyl-esters carried by lipoproteins induce the loss of body fat can affect Zucker fa/fa rats, since they are hyperphagic and could not eliminate excess energy through thermogenesis, two aspects essential for the slimming effect of oleoyl-estrone in normal rats. DESIGN: The rats were infused for 28 d (osmotic minipumps) with oleoyl-estrone in liposomes (Merlin-2) at a dose of 3.5 mmol/day.kg. SUBJECTS: Lean (L) and obese (O) Zucker rats. MEASUREMENTS: Body weight changes. Oxygen consumption, body composition (water, lipid, protein), nitrogen balance, plasma chemistry. RESULTS: Treatment resulted in loss of body weight: 12.0% (28 g) L, 9.4% (34 g) O, mainly due to fat: 37.5% (10.8 g) L, 11.7% (15.5 g) O and water, preventing further increases in body weight and fat storage. Untreated rats increased their body weight: 10.5% (24 g) L, 32.2% (101 g) O and lipid stores: 20.3% (5.9 g) L, 39.8% (49.0 g) O, making the differences more marked. On day 28, glucose levels were maintained in all groups; in L, triacylglycerols increased and total cholesterol decreased; O showed no changes in plasma composition. In all rats, food intake decreased with treatment, and heat production (oxygen consumption) was unchanged (L) or slightly decreased (O). Energy expenditure per unit of fat-free mass remained unchanged. Protein balance was maintained in all groups; slimming was achieved without loss of body protein. CONCLUSION: Treatment of genetically obese rats with oleoyl-estrone in liposomes (Merlin-2) results in sustained loss of body weight-mainly lipid, sparing protein-for up to 28 d, essentially preventing further increase in body weight and accumulation of lipid and protein. This is achieved through lower food intake and relatively small changes (if any) in energy expenditure.

Animals↗