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C Picó

Publications and source records attributed to C Picó.

31 records · Page 2Linked to original sources

Stabilization of the mRNA for the uncoupling protein thermogenin by transcriptional/translational blockade and by noradrenaline in brown adipocytes differentiated in culture: a degradation factor induced by cessation of stimulation?

The stability of the mRNA coding for the uncoupling protein thermogenin was investigated in mouse brown-fat cells differentiated in culture. After 7 days in culture, the cells were stimulated for 24 h with noradrenaline, and a high level of thermogenin mRNA was then observed. If noradrenaline treatment was continued, the mRNA level remained high, but, upon withdrawal of noradrenaline, the level decreased rapidly, with a half-life of only 2.7 h. The presence of transcriptional (actinomycin) or translational (cycloheximide) inhibitors prolonged the apparent half-life by about 50%. The presence of noradrenaline during transcriptional blockade led to a further stabilization of thermogenin mRNA. It was concluded that an induced (or short-lived) gene product is important for thermogenin mRNA degradation. Direct interaction of noradrenaline with the cultured brown adipocytes could apparently not mimic the paradoxical destabilization of thermogenin mRNA in vivo, previously observed in the cold-exposed mouse [Jacobsson, Cannon and Nedergaard (1987) FEBS Lett. 244, 353-356], indicating significant differences between the systems in vitro and in vivo.

Adipocytes↗

Blood cell to plasma gradients of amino acids in arterial and venous blood in fed and fasted rats.

Measurement of amino acid concentrations in blood cells and plasma, and the calculated blood cell to plasma gradients (C/P) from both afferent and efferent vessels to tissues, allowed evaluation of the effect of several tissues (splanchnic bed, skeletal muscle and kidney) on blood amino acid distribution in fed and starved rats. Combined effects of tissues and erythrocyte transport capabilities determined specific C/P values for each amino acid. For amino acids related to the L-system, the high capacity of this erythrocyte transport many buffer some C/P changes as an effect of tissue metabolism. For less permeable amino acids (like Asp and Glu) plasma changes were mainly responsible for changes in C/P values, whereas for other amino acids (such as basic amino acids) blood cells became the main determinants of C/P changes, mainly in starvation. In general, the role of erythrocytes in amino acid transport was enhanced in starvation.

Amino Acids↗

Blood amino acid compartmentation in obese rats is specifically altered in the iliac vein.

Amino acid concentration in blood cells and plasma and the calculated blood cell to plasma gradients (C/P) were measured in different blood vessels (aortic artery and portal, hepatic, iliac and renal veins) from both control and cafeteria diet obese rats. Essential amino acids are increased in plasma in all blood vessels in obese rats. The iliac vein was the only vessel in which cell concentration of amino acids, and mainly the mean of the combined non-essential amino acids, was affected by obesity. Only in the iliac vein were C/P values of the combined amino acids, including both essential and non-essential, significantly lower in obese versus control rats. These results also show that there are differences between sampling sites which should be noted in the design of physiological studies of amino acid metabolism.

Amino Acids↗

Opposite response to starvation of Trp/LNAA ratio in lean and obese Zucker rats.

Total blood and plasma free amino acids and plasma urea levels were studied in fed and 24 h fasted Zucker rats. In fed animals there were no differences between obese and lean rats in the overall essential and non essential blood free amino acids. However, starvation reduced blood amino acid levels in the obese animals compared to the lean group, mainly due to changes in the plasma compartment. The reduction of available amino acids from plasma in the obese rats during starvation affected most of the amino acids, including the branched chain amino acids, which showed higher levels in the fed situation than in lean rats. Of particular interest is the opposite response to starvation in lean and obese Zucker rats concerning the plasma ratio of tryptophan (Trp) to the large neutral amino acids (LNAA) which could be implicated in the alteration of food intake and energy expenditure characteristic of obesity.

Amino Acids↗

Regulation of rat erythrocyte L-glutamine, L-glutamate and L-lysine uptake by short term starvation.

1. The kinetic parameters (Km, Vmax and Kd) of L-glutamine, L-glutamate and L-lysine uptake by isolated red blood cells in fed and 24 hr starved rats have been determined. 2. L-Lysine and L-glutamine uptake was best fitted by a two transport component: a saturable component and a diffusion one. 3. Starvation brought about important decreases in the Km and Vmax for both L-lysine and L-glutamine uptake. 4. The Kd for L-glutamine showed a significant increase whereas that corresponding to L-lysine did not change by starvation. 5. L-Glutamate uptake adjusted to diffusion kinetics, with a Kd which did not change due to starvation. 6. It is concluded that the amino acid uptake showed specific regulation by starvation. 7. The mechanism involved is not dependent on protein synthesis--given the unnucleated nature of mammal red cells. 8. The magnitude of the changes observed in the uptake kinetic parameters may account for the extent of the blood amino acid pool changes as those produced in vivo over physiological limits.

Animals↗

Effect of diet-induced obesity on kinetic parameters of amino acid uptake by rat erythrocytes.

The effects of cafeteria diet-induced obesity upon in vitro uptake of L-Alanine, Glycine, L-Lysine, L-Glutamine, L-Glutamic acid, L-Phenylalanine and L-Leucine by isolated rat erythrocytes have been studied. The total Phe and Leu uptakes followed Michaelis-Menten kinetics. The Glu uptake was fitted to diffusion kinetics. The uptakes of Ala, Gly, Lys and Gln were best explained by a two-component transport: one saturable and one diffusion. Obesity increased the Km value for Ala, Gln and Leu, and the Vmax value for Ala, but decreased the Vmax for Lys. Kinetic parameters of Phe uptake were unaffected by obesity. In addition, the pseudo-first order rate constant (Vmax/Km) for Ala, Gly, Gln, Lys and Leu uptake decreased as a result of cafeteria diet-induced obesity. The Kd value for Ala, Gly, Gln and Glu decreased and that of Lys increased as result of obesity. These adaptations could, at least in part, explain alterations in amino acid distribution between blood cells and plasma related to overfeeding or obesity.

Amino Acids↗

A significant pool of amino acids is adsorbed on blood cell membranes.

It is well known that the amino acids in the blood are distributed between the plasma and inside the cells. This study was conducted to determine whether amino acids can be located adsorbed on blood cell membranes. The amino acid concentration in the deproteinized haemolysed blood was higher than that in the fraction of blood after removal of the blood cell membranes by centrifugation. These results showed that a pool of amino acids representing 21.1% of the whole blood cell amino acids was adsorbed on the blood cell membranes of adult Wistar rats. The non-polar amino acids showed high adsorption on the membrane, whereas out of the polar amino acid group, only the non-ionic amino acids did adsorb.

Adsorption↗

Alternating sequential endocrine therapy: tamoxifen and medroxyprogesterone acetate versus tamoxifen in postmenopausal advanced breast cancer patients.

The effects of tamoxifen (TAM) versus the alternating sequential combination of TAM plus medroxy-progesterone acetate (MPA) has been evaluated in 20 postmenopausal patients with advanced breast cancer in a randomized controlled trial. In the TAM arm, patients received 20 mg b.i.d. of TAM. In the TAM-MPA arm, patients received only 20 mg b.i.d. of TAM for 7 days and, on the following 7 days. TAM plus an oral daily dose of 500 mg of MPA, in alternating sequence. Objective tumor reduction was achieved in 22 (41%) of the 54 patients in the TAM arm and in 25 (43%) of the 58 patients in the TAM-MPA arm. With regard to the stabilization of disease, a significant difference was observed between patients treated with the TAM-MPA combination and those treated with TAM alone (47% vs 22%). The percentage of nonresponders was also significantly higher in the TAM group (37%) than in the TAM-MPA group (10%). The time to progression was significantly shorter for the TAM arm than for the TAM-MPA arm (median, 7 vs 15 months), but the duration of remission was not significantly different for either treatment.

Aged↗

Sustained changes in blood alpha amino nitrogen compartmentation during recovery from cafeteria feeding in rats.

We have previously reported that blood urea and blood cell amino acids levels are reduced in rats obese by feeding a palatable cafeteria diet. In order to distinguish whether these changes result from the altered diet, or from the obesity per se, we have studied cafeteria fed rats after returning to standard diet. As in previous studies, obesity induced by cafeteria feeding (for 90 days) was maintained when the cafeteria diet was removed and rats were fed standard diet only. After removal of the cafeteria diet, blood urea levels of 24 h starved obese rats were lower (23%) than those of starved control rats. Blood cell amino acid levels of obese were lower than control ones from day 50 onwards, during and after cafeteria feeding (21% lower on day 100 of life), and thus coincided with divergence of body weights; these differences were maintained despite removal of cafeteria diet. The effects of starvation on plasma amino acid levels were more marked in obese than control rats, during and after cafeteria feeding. Thus the effects on blood amino acids and urea levels in cafeteria diet induced obese rats are related to the obese status rather than to the diet composition.

Amino Acids↗

Short term starvation-induced changes in the kinetic parameters of rat red cell L-alanine and glycine uptake.

Na(+)-dependent L-Alanine and Glycine uptake by rat red blood cells were best fit to a common model of two transport components, saturable transport and diffusion. 24 hours of food deprivation provoked statistically significant increases of the Km and Vmax red cells L-Alanine uptake, whereas the diffusion constant did not change in response to starvation. The Glycine uptake kinetics poorly follows the L-Alanine pattern and no significant response to starvation can be outlined. The physiological meaning of these adaptations has to be related to short term food deprivation regulation, independent of protein synthesis in the erythrocytes. Such mechanisms could be important to account for the previously described changes in the distribution patterns of amino acids between the blood plasma and blood cell compartments in response to short term starvation.

Alanine↗

Tissue composition in persistent dietary obesity after early and adulthood overfeeding in the rat.

The objective of this study was to assess the effects of prolonged cafeteria-diet feeding on tissue composition in adult rats comparing those that had been overfed in early life and then in adulthood with a group that was only overfed in adulthood, and to determine whether any alterations were related to the high energy diet per se or to obesity. In addition to following the body weight changes in detail, tissue masses and composition were determined at selected points of this long term dietary experiment. The marked changes in body weight and tissue composition of cafeteria-fed obese rats were sustained for at least 84 days after returning to the standard diet, and the obesity was exaggerated if these animals were pre-exposed to the palatable diet in early life. Three patterns of tissue composition in response to cafeteria feeding could be discerned: Liver and brown adipose tissue developed cell hypertrophy without apparent hyperplasia. In contrast, the retroperitoneal white adipose depot developed hyperplasia whereas the intestine and kidneys were not associated with marked changes in lipid composition. These adaptations were not recovered to control levels by prolonged standard diet feeding. Previous obesity influenced the adaptations in adipose tissue during the subsequent return to standard diet feeding, and differences between cafeteria-induced obese animals became more apparent when the cafeteria diet was removed. These results indicated the important effects of early dietary experience in subsequent responses to overfeeding.

Adipose Tissue↗

[Nutrigenomics and obesity].

Obesity is a multifactorial disorder affected by multiple genetic and environmental factors, in particular nutrients, and their interrelationships. Increasing knowledge of the genes and molecules involved in the development of obesity is paving the way for new methods of obesity control. In this sense, Nutrigenomics--which represents a new approach in nutrition research that joints the application of powerful functional genomics technologies, bioinformatics and molecular biology with more traditional methodologies--may orientate the design and development of new functional foods for obesity, based on the scientific knowledge of the impact of specific nutrients on the mammalian body weight control system and their mechanisms of action.

Adipocytes↗