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Biomedical subjects

X Remesar

Publications and source records attributed to X Remesar.

At least 73 records · Page 4Linked to original sources

Amino acid nitrogen handling by hind leg muscle of the rat during exercise.

The arterio-venous differences and balance of amino acids across the hind leg of rats were measured during an intense bout of exercise in a treadmill, as well as in the subsequent recovery period. The size and composition of muscle amino acid pool were also determined using another series of animals. Finally, the amino acid composition of hind leg protein was determined and computed. During intense exercise and recovery, the muscle was a net contributor of amino acids to the bloodstream, the rates being higher during exercise than in recovery. This efflux was not only due to changes in pool size, but implied the hydrolysis of protein, in the range of 20-25 micrograms.min-1.g-1 during exercise. Branched chain amino acids were metabolized during exercise, but mainly during recovery. During exercise, there was also an increase in alanine and glutamine pool buildup and efflux. In conclusion, the data presented show that protein--and amino acid--metabolism in the exercising muscle are not as dormant as usually accepted, because branched chain amino acids are actively oxidized and the efflux of alanine, glutamine and other amino acids is maintained thanks to the net hydrolysis of protein.

Amino Acids↗

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↗

Carbohydrate handling in the hind leg muscle of exercising rats.

The arterio-venous concentrations of oxygen, glucose and lactate, as well as blood flow and muscle levels of lactate, glucose, hexose-phosphates and glycogen of rat hind leg muscle were determined under basal conditions and under mild and intense exercise, as well as during post-exercise recovery. During intense exercise and fatigue glycogen is practically exhausted, providing glycosyl residues to the hexose-phosphates pool in addition to increased glucose uptake from the blood. The result is the production of huge amounts of lactate, which accumulates in muscle and the skin, and buildup the arterial concentrations. During recovery lactate is slowly disposed of, and the muscle takes up large amounts of glucose which is stored into glycogen, with fully reinstated glucose oxidation. The data shown suggest that the shift from oxidative to mainly anaerobic utilization of glucose is not as streamlined as is usually assumed, since the results found here hint at the wasteful utilization of glycogen-derived hexose skeletons for other synthetic pathways. Glucose, nevertheless, is of paramount importance as energy staple to sustain untrained intense exercise in the rat.

Animals↗

Amino acid metabolism in the kidneys of genetic and nutritionally obese rats.

The ability of the kidney to take up and/or release amino acids has been determined in two models of obesity in Zucker rats, one genetic and the other nutritional (diet-obese). There was a noticeable increase in gluconeogenic amino acids in the arterial blood of diet-obese animals whereas the genetically obese rats showed small variations in the levels of these amino acids. There were significant decreases in renal Gly and Ser, only in the genetically obese rats. Genetically obese animals showed an increase in Glutamine synthetase activity. The uptake and/or release of amino acids showed important variations between the groups. The diet-obese group exhibited greater variation, since this group took up Glu, Ala, Gy, Phe and Citrulline and released Gln, Ser, Arg and Tyr. Genetically obese rats took up Gln, His and Taurine and released Ser. These different patterns may be related to variations in the whole body metabolic rate, since the diet-obese group was more active than the genetically obese group.

Alanine Transaminase↗

3-Hydroxybutyrate co-infused with noradrenaline decreases resulting plasma levels of noradrenaline in Wistar rats.

Pentobarbital-anaesthetized male Wistar rats were infused with 6microgkg-1min-1 of noradrenaline. The infusion was supplemented with 8.5 mgkg-1min-1 of D-3-hydroxybutyrate (3-OHB) for 15 min in order to determine its effect on the adrenergic response of the rat. Plasma levels of noradrenaline rose to a plateau of approximately 50 nmoll-1 with infusion. In the group infused with noradrenaline alone, noradrenaline levels were maintained for 1h. Supplementation with 3-OHB induced a decrease in plasma noradrenaline level that was inversely correlated with 3-OHB level. Aortic and interscapular brown adipose tissue temperatures increased with noradrenaline infusion, but the rise was arrested by 3-OHB; replacing 3-OHB with glucose had no effect. Infusion of saline, glucose or 3-OHB in the absence of noradrenaline did not induce a rise in temperature in either tissue. Blood 3-OHB concentration increased to 1.2 mmoll-1 during 3-OHB infusion, decreasing rapidly at the end of infusion. Blood glucose levels increased with noradrenaline infusion; the presence of high 3-OHB levels decreased glucose concentration. The effects observed were transient and dependent on 3-OHB concentration; these effects may help explain most of the other effects of noradrenaline described here. The role of 3-OHB as a regulator of adrenergic responses seems to be part of a complex fail-safe mechanism which prevents wasting.

3-Hydroxybutyric Acid↗

Muscle blood flow during intense exercise in the obese rat.

Tissue blood flow has been measured in Zucker lean and obese rats during treadmill exercise and later recovery, by using a fluorescent-dyed latex microsphere method. The procedure used allowed up to six different timed blood flow measurements in the same animal. Exercise resulted in grossly increased muscle blood flow, compensated by lowered intestinal and liver irrigation. At the onset of fatigue, and during early recovery, liver portal blood flow increased in detriment of muscle. Obese rats showed a similar pattern, but their intestinal and hepatic blood flow was maintained during recovery, in contrast with lean rats. In obese - but not in lean - rats, skin blood flow increased in post-exercise recovery to disposal of excess heat hampered by blubber insulation. Metabolic inability to recover markedly affects post-exercise haemodynamics in Zucker obese rats, thus prolonging the consequences of fatigue.

Animals↗

3-Hydroxybutyrate decreases noradrenaline affinity for rat erythrocyte ghost beta 2-adrenergic receptors.

The effects of physiological levels of 3-hydroxybutyrate on noradrenaline binding to rat erythrocyte membranes were studied. The binding of noradrenaline to membranes was determined by measuring the union of 3H-noradrenaline in the presence of varying concentrations of 3-hydroxybutyrate. Scatchard plots of the results were used to determine that 3-hydroxybutyrate provoked a loss of affinity of the beta 2-adrenergic receptors for adrenaline. Thus high (but physiological) 3-hydroxybutyrate levels can lower the binding of the catecholamine, thus diminishing the extent or intensity of adrenergic-driven responses.

3-Hydroxybutyric Acid↗

Oleoyl-estrone induces the loss of body fat in rats.

OBJECTIVE: Four experiments were devised to test the possible role of estrone fatty esters as adipose tissue signals carried by the blood within lipoproteins. DESIGN: Oleoyl-estrone was synthesized and incorporated in liposomes; it was administered i.v. (to mimic lipoprotein delivery) for 14-day periods using implantable osmotic minipumps. The study included the finding of oleoyl-estrone in blood lipoproteins, the correlations of the effects of body weight to the dose and the uptake of labelled oleoyl-estrone by tissues, its internalization and disposal. SUBJECTS: Normal-weight Wistar female rates were used. Pooled human blood was used as source of HDL3. MEASUREMENTS: Oleoyl-estrone was identified in rat white adipose tissue and in human blood HDL3 lipoprotein fraction. Changes in body weight, food intake, oxygen consumption, respiratory quotient and nitrogen balance were measured in chronically injected rats. The uptake and hydrolysis of oleoyl-estrone by tissues was also determined following its acute administration. RESULTS: Oleoyl-estrone induced a dose-dependent loss of weight, with decreased food intake. In 14 days, and compared with controls at the end of this period, a dose of 0.78 mumol/day induced the loss of 16.4 +/- 5.5% of body weight; the difference was maximal for doses of 15 mumol/day or higher: 24.7 +/- 3.1%. Under oleoyl-estrone treatment, body protein was preserved (positive nitrogen balances) and fat stores were wasted: lowered respiratory quotient, and deficit in energy balance; a dose of 0.78 mumol/day induced the loss of 9.6 +/- 2.2 g of total body lipids in 14 days. Most of oleoyl-estrone taken up by tissues was hydrolysed; however, in part it reached intact the cell nucleus of incubated adipocytes. Oleoyl-estrone effects were different from those of free estrone. CONCLUSION: A lipophilic pathway for oleoyl-estrone transport by lipoproteins is postulated, allowing chemical communication between tissues. Oleoyl-estrone may be directly involved in the control of body weight.

Adipocytes↗

Brown adipose tissue temperature in lean and obese rats during exercise.

OBJECTIVE: To determine the extent to which brown adipose tissue (BAT) heat output is influenced by treadmill exercise. DESIGN: The aortic blood core and interscapular BAT temperatures were recorded continuously during a short bout of intense exercise (different for each rat stock) in a treadmill and the ensuing 1-h recovery, sampling blood flows at timed intervals. SUBJECTS: Conscious Wistar, Zucker lean and Zucker obese rats. MEASUREMENTS: Aortic and interscapular BAT temperatures and tissue blood flow. RESULTS: Basal mean temperatures were highest for Wistar. Exercise provoked increases in aortic core temperatures in all three groups, slowly cooling off during recovery. Exercise and/or fatigue induced increases (vs aortic core temperature) of IBAT temperature. The effects were less marked in obese rats. CONCLUSION: Increases in BAT temperatures induced by exercise were counteracted by parallel decreases in blood flow, resulting in insignificant losses of heat from intarscapular BAT during exercise and recovery both in lean and obese rats.

Adipose Tissue, Brown↗

Adipose tissue extraction of circulating insulin in anaesthetized Zucker obese rats.

OBJECTIVE: To determine whether adipose tissue removes a significant proportion of circulating insulin in the obese rat in vivo. DESIGN: Blood samples were obtained from the carotid artery and the venous side of hind leg muscle, epididymal fat pads and liver (portal and suprahepatic veins), they were used for estimation of insulin disappearance across the tissue. SUBJECTS: Anaesthetized Zucker lean (Fa/?) and obese (fa/fa) adult male rats. MEASUREMENTS: Blood flow, glycaemia and insulinaemia. RESULTS: In lean rats, the liver accounted for practically all insulin extraction (498 +/- 149 fmol.s-1), removing more than half of the portal insulin in a single pass. In the obese rats, the liver extracted a similar amount in absolute terms (397 +/- 108 fmol.s-1), representing only 16% of portal insulin. In the hind leg muscle of both groups and in the adipose tissue of lean rats, insulin balances were not different from zero; but in obese rats, adipose tissue extracted a similar amount of insulin (405 +/- 127 fmol.s-1) to that removed by the liver. CONCLUSIONS: In the Zucker obese rat, peripheral adipose tissue removes as much insulin from the blood as the liver does, in contrast with lean rats, in which the latter is responsible for practically all insulin extraction.

Adipose Tissue↗

Estrogen effects on blood amino acid compartmentation.

The present paper focuses on the study of blood amino acid compartmentation in healthy men (lean and obese) and women, with special emphasis on the estimation of the recently described blood-cell adsorbed amino acid pool. The wide range of changes found in this pool on comparing different physiological situations may be attributable to its proposed characteristic high dynamism on the one hand, but also to the influence of other factors such as hormones. Along these lines, the sex- and obesity-linked variations found here in human blood led to the speculation as to whether these differences could be related to the influence of estrogens. This hypothesis was further tested by chronically treating a group of male rats with estrone and checking their subsequent blood amino acid compartment changes (which yielded a greater difference in the adsorbed pool). From the overall results obtained it may be concluded that the higher production of estrogens in women and obese men affects amino acid availability to the tissues by modulating the blood-cell adsorbed amino acid pool through a mechanism that is, at present, unknown.

Adult↗

Starvation-induced increase of hepatic alanine uptake is related to changes in sensitivity to SH-group reagents.

Changes in L-alanine transport in plasma membrane vesicles from livers of control and 24- and 48-h starved adult rats and the sensitivity of alanine uptake to sulfhydryl group reagents [N-ethylmaleimide (NEM) and p-chloromercuribenzenesulfonate (p-CMBS)] were studied. The portal concentration of certain amino acids was measured, and the relationship between L-alanine transport kinetic parameters and amino acid levels was analyzed. Starvation only induced a decrease in portal concentration of these amino acids that are mainly carried by Na(+)-dependent systems (85 and 61% for 24- and 48-h starved rats, respectively). Portal alanine concentration was lower in 24-h starved animals than in control rats (370 vs. 587 microM) and further decreased after 48 h of fasting (228 microM). Starvation induced an increase in maximum velocity (Vmax) values of Na(+)-dependent L-alanine transport (7.19, 8.97, and 12.38 pmol.U 5'-nucleotidase-1.10 s-1 for control and 24- and 48-h starved rats, respectively) with slight, but not significant, changes in the apparent Michaelis constant (Km) values (3.35, 2.63, and 2.20 mM for control and 24- and 48-h starved rats, respectively). Portal alanine showed a directly close correlation with Km values and inverse with Vmax values. The mean affinity constant values for the effects of NEM and p-CMBS on Na(+)-dependent L-alanine transport were lower in 48- (2.57 and 0.13 mM, respectively) and 24-h starved rats (3.59 and 0.32 mM, respectively) than in control rats (8.56 and 0.59 mM, respectively) and showed a directly strong correlation with kinetic characteristics of L-alanine transport and portal alanine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloromercuribenzenesulfonate↗

Rat insulin turnover in vivo.

Zucker lean and obese rats were injected under pentobarbital anesthesia with 125I-labeled insulin; at timed intervals from 30 to 120 sec, blood samples were extracted and used for the estimation of insulin levels by RIA. A group of rats from each series was maintained under a constant infusion of noradrenaline. For each insulin determination, a duplicate blood sample containing the same amount of insulin as that used in the RIA, but without the radioactive label, was used as a blank for insulin measurement. The radioactivity in these tubes was then used for the measurement of insulin label per ml blood. From plasma label decay curves and insulin concentrations, the insulin pool size, half-life, and rate of degradation were calculated. Obese rats had higher insulin levels (2.43 nM) and showed less effect of noradrenaline than their lean counterparts, in which insulin distribution volume shrank with noradrenaline treatment. The half-life of plasma insulin was similar in all groups (range, 226-314 sec). Pool size and overall degradation rates were higher in obese (198 femtokatals) than in lean rats (28 femtokatals). It is postulated that obese rats synthesize and cleave much more insulin than lean controls despite their higher circulating levels of insulin.

Animals↗

Insulin degradation by adipose tissue is increased in human obesity.

White adipose tissue samples from obese and lean patients were used for the estimation of insulin protease and insulin:glutathione transhydrogenase using 125I-labeled insulin. There was no activity detected in the absence of reduced glutathione, which indicates that insulin is cleaved in human adipose tissue through reduction of the disulfide bridge between the chains. Obese patients showed higher transhydrogenase activity (per U tissue protein wt, per U tissue wt, and in the total adipose tissue mass) than the lean group. There is a significant correlation between the activity per U tissue wt, and protein and total activity in the whole adipose tissue with respect to body mass index, with a higher activity in obese patients. The potential of insulin cleavage by adipose tissue in obese patients was a mean 5.6-fold higher than that in controls. The coexistence of high insulinemia and high cleavage capability implies that insulin secretion and turnover are increased in the obese. Thus, white adipose tissue may be crucial in the control of energy availability through modulation of insulin cleavage.

Adipose Tissue↗

Hindleg muscle energy and substrate balances in cold-exposed rats.

Rats chronically cannulated in the carotid artery and the muscular branch of the femoral vein were subjected to a cold (4 degrees C) environment for up to 2 h. The changes in blood flow (measured with 46Sc microspheres) and arterio-venous differences in the concentrations of glucose, lactate, triacylglycerols and amino acids allowed the estimation of substrate (and energy) balances across the hindleg. Mean glucose uptake was 0.28 mumol min-1, mean lactate release was 0.33 mumol min-1 and the free fatty acid basal release of 0.31 mumol min-1 was practically zero upon exposure to the cold; the initial uptake of triacylglycerols gave place to a massive release following exposure. The measurement of PO2, PCO2 and pH also allowed the estimation of oxygen, CO2 and bicarbonate balances and respiratory quotient changes across the hindleg. The contribution of amino acids to the energy balance of the hindleg was assumed to be low. These data were used to determine the sources of energy used to maintain muscle shivering with time. Three distinct phases were observed in hindleg substrate utilization. (1) The onset of shivering, with the use of glucose/glycogen and an increase in lactate efflux. Lipid oxidation was practically zero (respiratory quotient near 1), but the uptake of triacylglycerols from the blood remained unchanged. (2) A substrate-energy shift, with drastically decreased use of glucose/glycogen, and of lactate efflux; utilization of triacylglycerol as practically the sole source of energy (respiratory quotient approximately 0.7); decreasing uptake of triacylglycerol and increased tissue lipid mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Treadmill chamber for studies of respiratory gas exchange in the rat during exercise.

A treadmill for studying gas exchange in small mammals during exercise is presented. The system consists of a motor-driven running mat enclosed in a gastight chamber that receives a measured flow of air from a compressed air cylinder. The gas flow and temperature, pressure and instantaneous gas composition of the chamber (oxygen, carbon dioxide and water) are measured continuously and the data are computed to include the effects on chamber atmosphere of the rat activity, either running or at rest. The system is completed with a shock delivery grid that stimulates the rat to run. The calculations are based on the changes in the composition of the gas in the chamber (constantly stirred by a small electric fan) induced by the rat instead of relying on the alterations induced in the outflowing gas. The consumption of oxygen, and production of carbon dioxide and water by the rat are computed in real time, giving a very fast response to physiological change induced by exercise. The chamber is custom-made from an aluminium block and a plexiglass lid; all other components are available commercially. The system, as described, allows for a detailed analysis of respiratory gas (and water) exchange by rats under varying exercise conditions, there is practically no time lag between changes in respiratory gases and the detection of these changes, and the buffering effect of the chamber size is practically eliminated because of the calculation approach used.

Animals↗

Splanchnic amino acid pattern in genetic and dietary obesity in the rat.

The study of intestinal and hepatic uptake of amino acids by obese rats has been the main objective of this work. The obese animals used were either from genetic or from nutritional basis. In fed state, the intestinal release of amino acids was higher in obese animals than in lean ones (around the double values), but nutritionally and genetically obese rat showed a related pattern, specially for the case of alanine (increased release in relation to controls by a factor of 10). The higher alanine release by intestine is not reversed by 12-h food deprivation. The hepatic availability was also higher in obesity models than in lean animals (increases over 30%). However, the hepatic uptake was increased in genetically obese animals (more than 35%) and decreased in nutritionally obese animals (more than 40%), especially due to alanine uptake (2419, 1100 and 3794 nmols/min/g protein in lean, Diet-ob and fa/fa animals respectively). In obese animals the food deprivation tended to normalize the hepatic uptake of alanine. The differences in alanine uptake between both types of obesity may reflect the differences of urea synthesis.

Amino Acids↗