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Biomedical subjects

M M Grasa

Publications and source records attributed to M M Grasa.

23 records · Page 2Linked to original sources

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↗

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↗

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↗

Effect of the slimming agent oleoyl-estrone in liposomes on the body weight of rats fed a cafeteria diet.

Weaned lean Zucker rats, 21-days old, were fed a cafeteria diet for 70 days. The cafeteria diet-obese rats were infused for 28 days (using miniosmotic pumps) with oleoyl-estrone in liposomes (Merlin-2) at a dose of 3.5 mmol/day.kg. Treatment resulted in loss of body weight: 11.6% (32 g), mainly due to fat: 20.0% (8.8 g), protein 5.2% (2.0 g) and water, preventing further increases in body weight and fat storage. Untreated rats increased their body weight: 7.6% (20 g), lipid: 10.5% (4.2 g) and protein: 13.2% (4.8 g). Plasma glucose, urea, triacylglycerols and cholesterol practically did not change with treatment. Merlin-2 decreased energy intake (to 83.7%) and energy output (to 87.7%, oxygen consumption). Decreases in nitrogen intake were partly compensated by higher digestive efficiency in treated rats. The size of the nitrogen gap was higher in treated rats than in controls. Essentially, protein balance was maintained and slimming was achieved with a minimal loss of body protein. Treated rats selected less carbohydrate, in particular sugars, in their diet than controls, but consumed practically the same protein and lipid. Treatment of cafeteria diet-fed rats with oleoylestrone in liposomes results in sustained loss of body weight--mainly lipid--for up to 28 days. Nitrogen balance is maintained overall. This is achieved through lower food intake--mainly of sugars--and less marked changes in energy output.

Animals↗

Rats receiving the slimming agent oleoyl-estrone in liposomes (Merlin-2) decrease food intake but maintain thermogenesis.

Oleoyl-estrone given i.v.--incorporated in liposomes to mimic lipoprotein delivery--(Merlin-2) to normal weight rats, induces a dose-dependent weight loss. Analysis of body composition showed that body protein concentration was preserved and fat stores wasted. The respiratory quotient was consistent with the massive oxidation of body fat, since the diet contained practically no lipid. Appetite was affected by Merlin-2, and thus food intake showed a transient decrease. But oxygen consumption (and basal metabolic rates) was kept practically unchanged at the levels of the controls, i.e. higher than needed to oxidize the food ingested during the weight loss period. Brown adipose tissue uncoupling protein levels were proportionally preserved with a 2-week treatment, but it lost a substantial amount of lipid. In conclusion, Merlin-2 is a slimming agent with considerable potential given its powerful fat-wasting action, since it maintains thermogenesis despite lowered energy intake.

Adipose Tissue↗