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Biomedical subjects

F Villarroya

Publications and source records attributed to F Villarroya.

At least 55 records · Page 3Linked to original sources
PubMed1988

Iodothyronine 5'-deiodinase activity and thyroid hormone content in brown adipose tissue during the breeding cycle of the rat.

Brown adipose tissue iodothyronine 5'-deiodinase activity is significantly lower in 17-day pregnant rats compared with virgin controls and remains low during late pregnancy and lactation. It fully recovers with abrupt weaning, but only partially with spontaneous weaning. Even though this profile of changes is remarkably in step with the known pattern of modifications in brown fat thermogenesis during the breeding cycle, the lowered iodothyronine 5'-deiodinase activity appearing between days 15 and 17 of pregnancy occurs earlier than the reduction in brown adipose tissue thermogenesis. Brown fat 3,3',5-tri-iodothyronine content is also reduced in late pregnant, early and mid-lactating rats, most probably as a consequence of the lowered 5'-deiodination of thyroxine in situ. Acute insulin treatment increases brown fat iodothyronine 5'-deiodinase activity in virgin animals as well as in late-pregnant and lactating rats, despite the lowered basal enzyme activity levels in the latter groups. Thus an impaired response to insulin in brown fat does not appear to be a factor leading to the lowered iodothyronine 5'-deiodinase activity during late pregnancy and lactation.

Adipose Tissue, Brown↗
PubMed1988

Evidence for a differential physiological modulation of brown fat iodothyronine 5'-deiodinase activity in the perinatal period.

Brown adipose tissue iodothyronine 5'-deiodinase increases progressively in fetuses from the day 17 of pregnancy on, it reaches peak values on the 20th day of gestation and declines in the last days of fetal life as well as during the first day of life. Birth of premature fetuses causes a sudden drop in the enzyme activity. Postmaturity is associated to a decrease in brown fat 5'-deiodinase similar to that found after birth in fetuses born at term. In the first hours of life brown fat iodothyronine 5'-deiodinase is essentially insensitive to the cold-stimulus. Present data indicates that, differently from adult rats, brown fat iodothyronine 5'-deiodinase activity during the perinatal period is dissociated from the thermogenic activity of the tissue. It is suggested that factors different from the action of the sympathetic nervous system may play a main role in brown fat iodothyronine 5'-deiodinase activity modulation in the fetal and neonatal life.

Adipose Tissue, Brown↗
PubMed1988

Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation.

The net uptake/release of glucose, lactate and amino acids from the bloodstream by the interscapular brown adipose tissue of control, cold-exposed and cold-acclimated rats was estimated by measurement of arteriovenous differences in their concentrations. In the control animals amino acids contributed little to the overall energetic needs of the tissue; glucose uptake was more than compensated by lactate efflux. Cold-exposure resulted in an enhancement of amino acid utilization and of glucose uptake, with high lactate efflux. There was a net glycine and proline efflux that partly compensated the positive nitrogen balance of the tissue; amino acids accounted for about one-third of the energy supplied by glucose to the tissue. Cold-acclimation resulted in a very high increase in glucose uptake, with a parallel decrease in lactate efflux and amino acid consumption. Branched-chain amino acids, however, were more actively utilized. This was related with a much higher alanine efflux, in addition to that of glycine and proline. It is suggested that most of the glucose used during cold-exposure is returned to the bloodstream as lactate under conditions of active lipid utilization, amino acids contributing their skeletons largely in anaplerotic pathways. On the other hand, cold-acclimation resulted in an important enhancement of glucose utilization, with lowered amino acid oxidation. Amino acids are thus used as metabolic substrates by the brown adipose tissue of rats under conditions of relatively scarce substrate availability, but mainly as anaplerotic substrates, in parallel to glucose. Cold-acclimation results in a shift of the main substrates used in thermogenesis from lipid to glucose, with a much lower need for amino acids.

Adipose Tissue, Brown↗
PubMed1988

Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe.

1. Studies on human brown adipose tissue require specific molecular probes. A human genomic library has been screened with a complementary DNA corresponding to the uncoupling protein (UCP) of rat brown adipose tissue mitochondria. 2. Two recombinant phages were isolated, carrying genomic sequences of human UCP. From them we have subcloned a 0.5 kilobase fragment. This fragment, H-Ucp-0.5, contained two intronic regions and two exonic regions. Exonic regions encoded a sequence of 84 amino acids which exhibited a strong homology with central domain at rat UCP. The organization of H-Ucp-0.5 was confirmed by SI mapping analysis. 3. A Southern analysis suggested that the gene is single type in the human, as it is in rodents. 4. In Northern analysis experiments, H-Ucp-0.5 detected a specific 1.8 kb mRNA in human brown adipose tissue obtained from six patients with phaeochromocytoma and from one patient with a hibernoma. This molecular probe is a new, sensitive and reliable tool with which to study human brown adipocytes.

Adipose Tissue, Brown↗
PubMed1988

Effects of maternal hypocaloric diet feeding on neonatal rat brown adipose tissue.

Hypocaloric diet (control diet diluted 1:1 with cellulose) feeding during pregnancy caused a reduction in the body weight of rat pups at birth whereas the main parameters of brown adipose tissue composition and thermogenic activity were unaffected. When prenatally underfed rat pups were nursed by untreated dams eating control diet during lactation, early (day 4 of life) and late (day 13 of life) neonatal body weight was rehabilitated and brown adipose tissue remained essentially unchanged. When prenatally underfed rat pups were nursed by dams that were fed with the hypocaloric diet during lactation, neonatal body weight continued lower at the two mentioned days of life and the overall thermogenic capacity of brown fat (GDP binding/g body weight) was substantially depressed. The reduction of the brown fat thermogenic capacity in these pups is mainly due to a hypotrophy of the mitochondrial component of the tissue as indicated by the lowered cytochrome oxidase activity. Results indicate that mild maternal underfeeding during lactation may depress brown adipose tissue thermogenic function in neonates whereas similar hypocaloric intakes during pregnancy did not alter brown fat thermogenic capacity.

Adipose Tissue, Brown↗
PubMed1987

Direct assessment of brown adipose tissue as a site of systemic tri-iodothyronine production in the rat.

Tri-iodothyronine (T3)production by interscapular brown fat was studied by measurements of arterio-venous differences and blood flow across the tissue in rats exposed to the following situations: controls, acute cold, chronic cold and starvation. Results demonstrate that brown adipose tissue is a source of systemic T3 in the rat and that the T3 release is modulated according to the physiological situation of the animal: increased in cold exposure and inhibited in starvation.

Adipose Tissue, Brown↗
PubMed1987

Iodothyronine 5'-deiodinase activity in rat brown adipose tissue during development.

Iodothyronine 5'-deiodinase activity in rat brown adipose tissue has a characteristic pattern of developmental changes that is completely different from that of the liver. Fetal brown fat exhibits an extremely high iodothyronine 5'-deiodinase activity that is approx. 10-fold that in adult rats. Even though brown fat iodothyronine 5'-deiodinase activity falls suddenly at birth, there is a new peak in the activity around days 5-7 of life, whereas it remains very low afterwards. Just after birth, brown adipose tissue iodothyronine 5'-deiodinase activity is already capable of stimulation by noradrenaline. The postnatal peak in brown fat iodothyronine 5'-deiodinase correlates with the known increase in the thermogenic activity of the tissue in the neonatal rat, thus reinforcing the suggestion that local 3',3,5-triiodothyronine generation could be an important event related to thermogenesis in brown adipose tissue. However, the high fetal activity was only slightly related to the thermogenic activity of brown fat. Moreover, the increased iodothyronine 5'-deiodinase activity of brown adipose tissue during fetal and neonatal life suggests a substantial contribution by brown fat in the overall extrathyroidal 3',3,5-triiodothyronine production in these physiological periods.

Adipose Tissue, Brown↗
PubMed1987

Reduced noradrenaline turnover in brown adipose tissue of lactating rats.

Brown adipose tissue properties as well as noradrenaline turnover in the tissue were determined in 15-day lactating rats and virgin controls. Brown adipose tissue thermogenic activity was reduced in lactating rats as shown by a decrease in weight, cytochrome oxidase activity and mitochondrial GDP-binding. The noradrenaline turnover rate was lower in brown adipose tissue from lactating rats. It is suggested that diminished sympathetic activity in brown adipose tissue may be a major cause of the reduced tissue thermogenic activity during lactation.

Adipose Tissue, Brown↗
PubMed1987

Glucose metabolism "in vitro" in brown adipose tissue from pregnant and lactating rats.

(U-14C)Glucose utilization has been studied "in vitro" in brown adipose tissue pieces from virgin, 20-day pregnant and 15-day lactating rats. Brown fat pieces from virgin rats increased their (U-14C)glucose utilization for (14C)CO2 production and for (14C)fatty acid and (14C)glycogen synthesis when insulin was present in the medium. Opposite changes were observed due to the presence of noradrenaline. Brown fat from late pregnant rats does not present any essential alteration in its capacity of metabolizing glucose and showed a pattern of responses to insulin and noradrenaline similar to that from virgins. Brown fat from mid lactating rats showed an intrinsic reduction in (U-14C)glucose utilization for oxidative pathways as well as for fatty acid synthesis, this reduction was present in all hormonal conditions. This data suggests a relationship between the lowered glucose metabolism and the known reduction in brown fat thermogenesis during mid lactation.

Adipose Tissue, Brown↗
PubMed1986

Impaired basal and noradrenaline-induced iodothyronine 5'-deiodinase activity in brown adipose tissue from pregnant and lactating rats.

Basal iodothyronine 5'-deiodinase activity is lowered in brown fat from 20-day pregnant, 5 and 15-day lactating rats when compared with virgin controls. Acute noradrenaline treatment caused a seven fold increase in 5'-deiodinase activity in brown fat from virgin control rats. Late pregnant and lactating rats showed a reduction in noradrenaline-induced 5'-deiodinase activity in brown adipose tissue and the maximum impairment was observed in 15-day lactating rats. Lowered 5'-deiodinase activity in brown fat during late pregnancy and lactation correlates with the known reduction in the thermogenic activity of the tissue during these situations and agrees with the proposal that the rate of 3,5,3'-triiodothyronine generated in situ because of thyroxine 5'-deiodination could be an essential event related to thermogenesis in brown fat. Even though the relationship between 3,5,3'-triiodothyronine generation in the tissue and the specific thermogenic mechanisms of brown fat is unknown, present results indicate a close link between the thermogenic and 5'-deiodinase activities in physiological situations when brown adipose tissue needs to adapt to a low activity, such as that of the breeding cycle.

Adipose Tissue, Brown↗
PubMed1986

Sequential changes in brown adipose tissue composition, cytochrome oxidase activity and GDP binding throughout pregnancy and lactation in the rat.

The sequential appearance of changes in interscapular brown adipose tissue composition, cytochrome oxidase activity and GDP binding was studied throughout pregnancy and lactation in the rat. Brown adipose tissue was hypertrophied during pregnancy because of progressive lipid accumulation, whereas its mitochondrial component and GDP binding to brown fat mitochondria were unchanged. In early lactation (day 5) there was a decrease in the overall GDP binding to brown fat only because of the lower mitochondrial protein content. In late stages of lactation (days 10 and 15), the amount of tissue and its mitochondrial protein content were minimal and the GDP binding per mitochondrial protein decreased substantially. Scatchard analysis in day-15-lactating rats indicated a large decrease in GDP binding sites without any changes in affinity. It is concluded that the diminished thermogenic activity of brown fat in lactation is attained through changes at different structural levels of the tissue occurring in a characteristic sequential trend; first a reduction in its mitochondrial component, and only later, at mid-lactation, a decrease in the specific mitochondrial proton conductance pathway activity.

Adipose Tissue, Brown↗
PubMed1986

Brown adipose tissue activity in hypocaloric-diet fed lactating rats.

Hypocaloric diet feeding reduced the mitochondrial protein content and whole tissue GDP-binding in interscapular brown adipose tissue from both virgin and lactating rats. A reduction in brown fat lipoprotein lipase activity was also detected in underfed virgin and lactating animals. These results indicate that lactation in the rat, even though it produces a reduction in brown fat activity, does not impair the capacity of the tissue to respond to a diminished caloric intake by lowering its activity further.

Adipose Tissue, Brown↗
PubMed1986

Changes in brown adipose tissue lipoprotein lipase activity and lipogenesis rate during pregnancy and lactation in the rat.

Brown fat lipoprotein lipase activity did not change in the first two weeks of pregnancy whereas it decreased on day 18 of gestation and was lower during late pregnancy and lactation. Fatty acid synthesis rate, measured in vivo with (3H)H2O, showed a progressive increase until day 18 of gestation followed by a decrease on day 20 of pregnancy and a reduced lipogenesis rate throughout lactation. The early reduction in the pathways of fatty acid uptake and synthesis in brown fat during the breeding cycle of the rat suggests the possibility that a decline in the substrate supply was a factor contributing to the reduced thermogenic activity of brown adipose tissue after parturition.

Adipose Tissue, Brown↗
PubMed1985

Hepatectomy-nephrectomy effects in the pregnant rat and fetus.

Levels of circulating glucose, glycerol, and FFA concentrations were determined before and after hepatectomy-nephrectomy in 20 day pregnant rats and virgin controls. After evisceration, blood glucose levels decreased in a parallel way in both groups whereas in pregnant rats, the blood glycerol level increased less and plasma-FFA rose more than in controls. Maternal evisceration caused reduced blood glucose and enhanced glycerol levels in fetuses, whereas fetal plasma-FFA levels were unmodified. Results indicate that extrahepatic glucose utilization remained stable in the late pregnant rat. Fetal levels of circulating glycerol, but not of FFA, appeared directly dependent on maternal levels. It is proposed that under normal conditions, glycerol availability to the fetus is low, due to its preferential utilization by maternal gluconeogenic organs which reduced the amount available for possible placental transfer.

Animals↗
PubMed1985

Comparison of effects of different anticoagulants and sample handling procedures on rat insulin radioimmunoassay.

1. The effects of several potential inducers of artifacts on insulin RIA: use of anticoagulant (heparin, EDTA) versus clotting , repeated freezing/thawing and the presence of added ions (Ca2+, Zn2+) has been studied on a large uniform pooled sample of rat blood. 2. Repeated freezing and thawing resulted in a very significant loss of RIA insulin. 3. The use of heparin or added lipid (Intralipid) to serum samples resulted in lower insulin measurements, whereas low protein or EDTA addition resulted in higher values. The effect of EDTA was not a consequence of its sequestering of calcium or zinc, as their combined addition did not change the EDTA effect. 4. The use of individualized non-specific binding for actual insulin estimations did not correct most of the artifacts induced by the different treatments studied. 5. As a general conclusion, utmost care must be taken to prevent the incidence of these sources of error by referring the data to controls, avoiding the use of EDTA as well as taking into account the actual composition and handling of the samples when measuring their insulin levels.

Animals↗
PubMed1985

Similar metabolic response to acute ethanol intake in pregnant and non-pregnant rats either fed or fasted.

Plasma ethanol concentration 3 hr after its oral administration (3 g/kg body wt) did not differ in 20 day pregnant rats with virgin controls, and in both groups values were higher when studied after 24 hr fasted than when fed. In fed animals, blood glucose and liver glycogen concentrations were lower in pregnant than in virgin rats, whereas ethanol intake in both groups enhanced blood glucose levels, it reduced liver glycogen content only in virgins. In fetuses, maternal ethanol intake enhanced blood glucose levels. In fasted animals, ethanol intake decreased blood glucose levels in pregnant and virgin animals but did not affect these levels in fetuses. Ethanol intake enhanced beta-hydroxybutyrate/acetoacetate ratio similarly in blood of pregnant and virgin rats when either fed or fasted, and it produced the same change in fetuses from fasted mothers. Results indicate that the metabolic response to acute ethanol does not differ between pregnant and non-pregnant animals, and it is proposed that fetuses passively follow the metabolic changes occurring in their mothers after receiving ethanol.

3-Hydroxybutyric Acid↗
PubMed1985

Effects of chronic ethanol treatment on glucose tolerance, insulin response and circulating metabolites in the pregnant rat.

The effects of chronic ethanol treatment on intravenous glucose tolerance and insulin response in non-pregnant and pregnant rats were studied. Basal circulating glucose, insulin, and ketone bodies levels were also determined during the treatment. Basal blood glucose concentration did not change during the ethanol treatment whereas plasma insulin levels were lower at the beginning of gestation and at the 15 and 18 days of pregnancy in ethanol-treated rats. Blood beta-OH-butyrate levels were higher and acetoacetate concentrations unchanged during the ethanol treatment, resulting in augmented beta-OH-butyrate/acetoacetate ratio. Intravenous glucose tolerance was not modified in ethanol-treated rats whilst the associated insulin response was lower in both non-pregnant and pregnant ethanol-treated rats. Data show that ethanol treatment during pregnancy alters glucose-insulin relationships despite being associated with unchanged maternal glycemia.

3-Hydroxybutyric Acid↗