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I Rafecas

Publications and source records attributed to I Rafecas.

At least 19 recordsLinked to original sources
PubMed1998

Formaldehyde derived from dietary aspartame binds to tissue components in vivo.

Adult male rats were given an oral dose of 10 mg/kg aspartame 14C-labelled in the methanol carbon. At timed intervals of up to 6 hours, the radioactivity in plasma and several organs was investigated. Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to protein. Label present in liver, plasma and kidney was in the range of 1-2% of total radioactivity administered per g or mL, changing little with time. Other organs (brown and white adipose tissues, muscle, brain, cornea and retina) contained levels of label in the range of 1/12 to 1/10th of that of liver. In all, the rat retained, 6 hours after administration about 5% of the label, half of it in the liver. The specific radioactivity of tissue protein, RNA and DNA was quite uniform. The protein label was concentrated in amino acids, different from methionine, and largely coincident with the result of protein exposure to labelled formaldehyde. DNA radioactivity was essentially in a single different adduct base, different from the normal bases present in DNA. The nature of the tissue label accumulated was, thus, a direct consequence of formaldehyde binding to tissue structures. The administration of labelled aspartame to a group of cirrhotic rats resulted in comparable label retention by tissue components, which suggests that liver function (or its defect) has little effect on formaldehyde formation from aspartame and binding to biological components. The chronic treatment of a series of rats with 200 mg/kg of non-labelled aspartame during 10 days resulted in the accumulation of even more label when given the radioactive bolus, suggesting that the amount of formaldehyde adducts coming from aspartame in tissue proteins and nucleic acids may be cumulative. It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.

Administration, Oral↗
PubMed1998

Plasma leptin turnover rates in lean and obese Zucker rats.

Conscious female adult lean and obese Zucker rats were injected through the jugular vein with radioactive iodine-labeled murine leptin; in the ensuing 8 min, four blood samples were sequentially extracted from the carotid artery. The samples were used in a modified RIA for leptin, in which paired tubes received the same amount of either labeled or unlabeled leptin, thus allowing us to estimate both leptin levels and specific radioactivity. The data were used to determine the decay curve parameters from which the half-life of leptin (5.46 +/- 0.23 min for lean rats and 6.99 +/- 0.75 min for obese rats) as well as the size of its circulating pool (32 pmol/kg for lean rats and 267 pmol/kg for obese rats) and the overall degradation rate (96 fkat/kg for lean rats and 645 fkat/kg for obese rats) were estimated. These values are consistent with the hormonal role of leptin and the need for speedy changes in its levels in response to metabolic challenge.

Animals↗
PubMed1997

Is leptin an insulin counter-regulatory hormone?

Leptin, the product of the ob gene, controls appetite through the hypothalamus and may affect many other tissues because of the widespread distribution of its receptors. Leptin is synthesized by white adipose tissue (WAT) under conditions of high energy availability and insulin stimulus. Glucocorticoids enhance this synthesis and catecholamines hamper leptin production. Leptin diminishes insulin secretion by the pancreatic beta cells and induces insulin resistance. In fact leptin hampers insulin action on WAT itself in a negative feedback loop. The evidence acquired in studies on diabetics, starvation, refeeding and insulin and glucose clamps supports this interpretation, which may also explain part of the difficulties encountered by the current postulate that links leptin to WAT mass size signalling to the brain. Leptin may be, essentially, a counter-regulatory hormone limiting the insulin drive to store energy in the form of fat, its effects reaching from a decrease in food intake to lower insulin secretion and increased resistance to insulin and lower glucose uptake and fat synthesis by WAT.

Adipose Tissue↗
PubMed1997

Leptin.

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Animals↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

Management of dietary essential metals (iron, copper, zinc, chromium and manganese) by Wistar and Zucker obese rats fed a self-selected high-energy diet.

The balances and content of essential elements (iron, copper, zinc, chromium and manganese) in the body of Wistar, Zucker lean and Zucker obese rats fed a reference or cafeteria diet from day 30 to 60 after birth have been studied. Intestinal iron absorption compensated for low iron content of the cafeteria diet and the extra needs of growth and fat deposition. It can be assumed that the altered energy regulation processes that afflict the genetically obese rat are not directly related to altered iron metabolism. Obese Zucker rats had lower copper tissue concentrations than lean rats, but when fed a cafeteria diet the differences between Zucker rats strains disappear. This cannot be traced to large differences in diet copper concentration. A low diet availability of zinc--such as that of cafeteria-fed fa/fa rats--is easily compensated for by increasing absorption. So, as a consequence, we can conclude that genetic obesity did not impair zinc absorption. There was no deficit of zinc in any of the groups studied; the rats have enough capacity to extract zinc within a wide range of dietary concentrations. The absorption of dietary chromium was inversely proportional to its concentration. The ability to extract chromium from the diet and the very low urinary losses are a consequence of its scarcity in most dietary items. Despite wide variations in the manganese of the diets, the absorption rates were practically unchanged except for obese rats fed the cafeteria diet. It seems that this low absorptive capacity is enough to supply the rat with the manganese it needs, since a sizeable--but subjected to 8-fold-span variations--proportion is lost in the urine. This alone points towards a considerable excess of manganese in both diets studied. Obesity does not have a significant effect on the abilities to absorb and retain minerals, since these processes were more related to dietary availability. Management of essential metals by obese rats depends whether this condition is genetic or induced by diet. Most of the differences observed can be related to differences in diet concentration, to the excess fat content or different metabolic attitude to use substrates of obese animals. The data presented show that the cafeteria diet used adequately serves the mineral needs of the rat, since the rat adapts its absorbing and retaining strategies to match the dietary availability of these minerals.

Animals↗
PubMed1994

Effect of a cafeteria diet on energy intake and balance in Wistar rats.

The energy balance and nutrient selection strategies of 30-day-old Wistar rats offered a reference pellet and a seven-item cafeteria diet were studied in two consecutive 15-day periods: 30-45 and 45-60 days after birth. Cafeteria-fed rats grew faster, incorporating more fat and water, but a similar amount of protein to reference-fed animals. In the second 15 days all rats ate less and produced less heat than in the first 15 days. Reference-fed rats also deposited less energy in their bodies, in contrast to the tendency towards higher carcass energy deposition in cafeteria-fed rats. Cafeteria-fed rats selected much more fat and sugars than controls, with similar protein and less starch; in the second period studied, cafeteria-fed rats significantly increased their sugar consumption, with no change in fat or protein. It is suggested that the switch to selecting more sugars may be an essential factor in the shift towards increased fat deposition at the expense of heat production in cafeteria-fed rats.

Animals↗
PubMed1994

Whole-rat protein content estimation: applicability of the N x 6.25 factor.

The amino acid composition of the protein from three strains of rat (Wistar, Zucker lean and Zucker obese), subjected to reference and high-fat diets has been used to determine the mean empirical formula, molecular weight and N content of whole-rat protein. The combined whole protein of the rat was uniform for the six experimental groups, containing an estimate of 17.3% N and a mean aminoacyl residue molecular weight of 103.7. This suggests that the appropriate protein factor for the calculation of rat protein from its N content should be 5.77 instead of the classical 6.25. In addition, an estimate of the size of the non-protein N mass in the whole rat gave a figure in the range of 5.5% of all N. The combination of the two calculations gives a protein factor of 5.5 for the conversion of total N into rat protein.

Amino Acids↗
PubMed1993

Individual amino acid balances in young lean and obese Zucker rats fed a cafeteria diet.

The amino acid composition of the diet ingested by reference and cafeteria diet-fed lean and obese Zucker rats has been analyzed from day 30 to 60 after birth. Their body protein amino acid composition was measured, as well as the urinary and faecal losses incurred during the period studied. The protein actually selected by the rats fed the cafeteria diet had essentially the same amino acid composition as the reference diet. The mean protein amino acid composition of the rat showed only small changes with breed, age or diet. Cafeteria-fed rats had a higher dietary protein digestion/absorption efficiency than reference diet-fed rats. Obese rats wasted a high proportion of dietary amino acids when given the reference diet, but not on the cafeteria diet. In all cases, the amino acids lost as such in the urine were a minimal portion of available amino acids. In addition to breed, the rates of protein accretion are deeply influenced by diet, but even more by the age-or size-of the animals: cafeteria-fed rats grew faster, to higher body protein settings, but later protein accrual decreased considerably; this is probably due to a limitation in the 'blueprint for growth' which restricts net protein deposition when a certain body size is attained. Obese rats, however, kept accruing protein with high rates throughout. Diet composition--and not protein availability or quality--induced deep changes in amino acid metabolism. Since the differences in the absolute levels of dietary protein or carbohydrate energy ingested by rats fed the reference or cafeteria diets were small, it can be assumed that high (lipid) energy elicits the changes observed in amino acid metabolism by the cafeteria diet. The effects induced in the fate of the nitrogen ingested were more related to the fractional protein energy proportion than to its absolute values. Cafeteria-fed rats tended to absorb more amino acids and preserve them more efficiently; these effects were shown even under conditions of genetic obesity. There were deep differences in handling of dietary amino acids by dietary or genetically obese rats. The former manage to extract and accrue larger proportions of their dietary amino acids than the latter. The effects of both 'models' of amino acid management were largely additive, suggesting that the mechanisms underlying the development of obesity did not run in parallel to those affecting the control of amino acid utilization. Obesity may be developed in both cases despite a completely different strategy of amino acid assimilation, accrual and utilization.

Amino Acids↗
PubMed1993

Water balance in Zucker obese rats.

The water balance in Wistar, Zucker obese and Zucker lean rats, aged 60 days, was measured by determining the amount of water they drank, that contained in the solid food eaten, the water lost through urine and droppings, the net water accrued (estimated from the composition of the body and the daily increase in body weight), the measurement of the water vapour lost and the calculation of metabolic water production by means of the measurement of oxygen consumption, carbon dioxide production and protein oxidation in a 24 hr period. 1. Despite widely different body weights, all three groups of animals accrued a similar proportion of their daily water budget (4.3-4.9%, i.e. 1.2-1.4% of the total rat water mass). 2. Wistar and Zucker obese rats had a similar daily water budget despite very different body weights, lean Zucker rats had lower water budgets. 3. Obese and lean Zucker rats produced a more concentrated, and excreted much less urine (the highest urea concentration was found in obese rats) than Wistar rats. 4. The water lost in the droppings was in the same range as that in urine for obese rats, slightly less for lean Zucker rats and much less in Wistar rats. Obese rats produced a higher amount of stool with respect to the amount of food eaten than the lean animals studied. 5. The contribution of metabolic water to the daily water budget was a 23.6% for Zucker obese, 22.5% for Zucker lean and 15.9% for Wistar rats.

Animals↗
PubMed1993

Lipid synthesis: a thermogenic mechanism in cold-exposed Zucker fa/fa rats.

1. The oxygen consumption and carbon dioxide production of Wistar and Zucker lean (Fa/?) and obese (fa/fa) rats was measured at 4, 10, 20 and 30 degrees C. 2. There was a net synthesis of lipid at the expense of carbohydrate in Wistar rats at 20 degrees C, with active lipid oxidation at 4 degrees C, and increasing heat production at lower temperature. Zucker lean rats also showed this trend. 3. Zucker fa/fa rats synthesized lipid at 4, 10 and 20 degrees C, showing a less marked increase in heat production with lowering temperature. 4. It is postulated that Zucker obese rats synthesize lipids as a way to obtain residual metabolic heat to maintain their body temperature. This is part of a process--fully functional in Wistar and Zucker lean rats, and truncated in Zucker obese rats--in which liver lipogenesis can combine with brown adipose tissue lipolysis to generate enough heat to maintain body functions under a cold environment.

Animals↗
PubMed1993

Intestinal and hepatic nitrogen balance in the rat after the administration of an oral protein load.

The fate of a small oral dose of protein given to overnight-starved rats was studied. After 3 h, 62% of the protein amino acids had been absorbed. Most of the absorbed N went into the bloodstream through the portal in the form of amino acids, but urea and ammonia were also present. About one-quarter of all absorbed N was carried as lymph amino acids. The liver was able to take all portal free ammonia and a large proportion of portal amino acids, releasing urea. The hepatic N balance was negative, indicating active proteolysis and net loss of liver protein.

Amino Acids↗
PubMed1993

Methodological evaluation of indirect calorimetry data in lean and obese rats.

1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60-day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry. 2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters. 3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry. 4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance. 5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry of direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one-fifth of total energy produced in the three rat stocks. 6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked pattern. 7. The results obtained indicate that lean and obese rats can be studied using the same indirect calorimetry formulae provided that there is an adequate measure of protein oxidation and the composition of diet does not differ.

Amino Acids↗
PubMed1993

Dietary amino acid balances in young Wistar rats fed a cafeteria diet.

The amino acid composition of the diet ingested by reference and cafeteria diet-fed rats has been analyzed in Wistar rats from day 30 to 60 after birth. Body protein amino acid composition and the urinary and faecal losses were also measured. Cafeteria diet resulted in a higher proportion of amino acids extracted from the diet, although this diet had a very similar amino acid composition to that of the standard reference diet. The net rates of amino acid accretion into body protein were similar for cafeteria and reference diet-fed rats, resulting in a comparable net overall accumulation of protein. Urinary losses of amino acids were small, but higher for reference diet-fed rats. Cafeteria feeding leads to an essentially equal amino acid intake pattern to that resulting from the reference diet. In addition, cafeteria-feeding resulted in a similar amino acid nitrogen intake and practically equal amino acid availability, which is translated into higher net protein accrual and lower nitrogen losses in cafeteria-fed rats. It is postulated that the lower protein-energy proportion of the cafeteria diet--and not its amount in absolute terms--could trigger a series of amino acid-sparing mechanisms that eventually result in even higher amino acid availability, which leads to increased net protein deposition and a wider nitrogen gap.

Amino Acids↗