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Biomedical subjects

T Mampel

Publications and source records attributed to T Mampel.

At least 37 records · Page 2Linked to original sources

Inhibition of iodothyronine 5'-deiodinase by iopanoic acid does not block nuclear T3 accumulation during rat fetal development.

We studied the effect of iopanoic acid (IOP), an iodinated contrast medium, on iodothyronine 5'-deiodinase (5'D) and nuclear T3 content (nT3) in fetal tissues. In 18- and 20 day-old fetuses from control dams, nT3 was higher in interscapular brown adipose tissue (IBAT, 69 +/- 5 and 281 +/- 8 fmol/mg of DNA) than in brain (16 +/- 2 and 42 +/- 3 fmol/mg of DNA) or liver (5.6 +/- 1 and 27 +/- 2 fmol/mg of DNA). IOP administration (10 mg, twice daily) to pregnant rats on days 18 and 19 postconception significantly blocked 5'D activity in fetal IBAT and brain at day 20. Liver 5'D was not affected. The rise in nT3 was not modified by IOP treatment in IBAT, but it was enhanced in brain and liver of IOP-treated fetuses on day 20. In contrast, in adult rats, IOP treatment reduced IBAT nT3. Prolongation of IOP treatment until day 21 decreased fetal body weight on day 22 and inhibited IBAT 5'D. No change was produced in mitochondrial oxidative capacity, the subunit II of cytochrome oxidase, or uncoupling protein mRNA expression in IBAT from IOP-treated fetuses. Thus, the finding that IOP does not decrease the nT3 of fetal IBAT explains the lack of effect of IOP on uncoupling protein expression in fetuses, in contrast with the known decrease in adults. Present results also show that IOP increases nT3 in brain and liver, indicating a general incapacity of IOP to decrease nT3 in fetal tissues. It is concluded that the effects of IOP during fetal life differ from those in adults.

Adipose Tissue, Brown↗

Effects of cold environment on mitochondrial genome expression in the rat: evidence for a tissue-specific increase in the liver, independent of changes in mitochondrial gene abundance.

The abundance of the mitochondrially encoded mRNA for subunit II of cytochrome c oxidase (COII mRNA) increases in the liver of rats exposed to environmental cold stress (4 degrees C ambient temperature). Only transient increases or no changes in COII mRNA levels were observed in brown fat and soleus muscle respectively. The time course of the liver COII mRNA increase was compared with the effects of cold stress on mitochondrial 16S ribosomal RNA expression and indicated that cold induces a rapid (few hours) increase in the liver mitochondrial mRNA levels and high levels of both messenger and ribosomal RNA mitochondrial transcripts are present after a few days of cold exposure. No changes in mitochondrial DNA abundance relative to total cellular DNA were observed in the liver of rats at any time during cold stress. It is concluded that mitochondrial genome expression is specifically increased in the liver of cold-exposed rats through different mechanisms, independent of changes in mitochondrial genome abundance.

Acclimatization↗

Ontogeny of thyroid hormone receptors and c-erbA expression during brown adipose tissue development: evidence of fetal acquisition of the mature thyroid status.

We have determined the developmental changes in thyroid hormone receptor expression and thyroid hormone status in rat brown adipose tissue (BAT). The present study demonstrates that c-erbA alpha and -beta genes are expressed in the developing BAT. The 6.5-kilobase (kb) beta 1, 2.6-kb alpha 2, 5.5-kb alpha 1, and 6.6-kb alpha transcripts showed peak values on day 20 of fetal life. High affinity T3-binding sites were found in fetal BAT. Binding capacity was similar (18-day-old fetuses) or higher (20-day-old fetuses) than in postnatal or adult brown fat. In contrast, T3 receptors were scarce in fetal liver, and values in adult liver were similar to those in fetal BAT on day 20. The profiles of iodothyronine 5'-deiodinase, nuclear T3 content, and receptor occupancy also showed peak values in fetal BAT on day 20, but they were very low in fetal liver. Thus, BAT has already achieved complete maturation of its thyroid status on day 20 of gestational age. This highly tissue-specific developmental pattern is unique among other mammalian thyroid-sensitive tissues studied to date. Between days 18 and 20 of rat fetal development, there is a specific induction of the uncoupling protein gene expression, the main marker of differentiated adipocytes. The results suggest that thyroid hormones may be involved in the establishment of the differentiated phenotype of the brown fat cell in fetal life.

Adipose Tissue, Brown↗

Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue. Unaltered iodothyronine 5'-deiodinase activity is necessary for the response to environmental temperature at birth.

We have performed a sequential study on the abundance of the mRNA for uncoupling protein (UCP), subunit II of cytochrome-c oxidase (COII) and lipoprotein lipase in brown adipose tissue during the fetal and postnatal periods. Moreover, we have determined whether these parameters can be modulated by ambient temperature in the early hours after birth, and at which point in development this sensitivity first appears. UCP gene expression in the fetal and neonatal period has particular features when compared with overall mitochondriogenesis (COII mRNA expression) or with the expression of lipoprotein lipase mRNA. There is a specific induction of UCP gene expression between days 18 and 19 of pregnancy followed by a specific increase of UCP gene expression in utero and a further increase after birth. The acquisition of the physiological apparatus capable of the response to UCP and lipoprotein lipase gene expression to the environmental temperature is not achieved until the last day of fetal development. This result suggests that mechanisms of beta-adrenergic modulation of gene expression in brown fat are already established at birth. From an experiment on iopanoic acid treatment of pregnant mothers, it was concluded that iodothyronine 5'-deiodinase activity is not necessary for the expression of the mRNAs for UCP, COII and lipoprotein lipase in the fetus whereas it is necessary for the acquisition of temperature sensitivity to these parameters at birth.

Adipose Tissue, Brown↗

Lipoprotein lipase mRNA expression in brown adipose tissue: translational and/or posttranslational events are involved in the modulation of enzyme activity.

Lipoprotein lipase mRNA abundance in rat brown adipose tissue increases during the first 24 h of cold exposure. Lipoprotein lipase mRNA levels do not change in brown fat throughout pregnancy and lactation, whereas enzyme activity is significantly lowered. After 5 h of acute cold or noradrenaline administration there is a 2-fold increase in lipoprotein lipase mRNA abundance, whereas lipoprotein lipase activity is stimulated to more than 6-fold the basal values. It is concluded that translational and/or posttranslational mechanisms are involved in the noradrenergic modulation of lipoprotein lipase activity in brown fat.

Acclimatization↗

Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation.

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation.

Adipose Tissue, Brown↗

Iodothyronine 5'-deiodinase activity as an early event of prenatal brown-fat differentiation in bovine development.

Iodothyronine 5'-deiodinase activity appears to be a type I enzyme in bovine brown adipose tissue, on the basis of its high Km for 3,3',5'-tri-iodothyronine ('reverse T3') (in the micromolar range) and sensitivity to propylthiouracil inhibition. This enzyme activity is already detectable in perirenal adipose tissue of bovine fetuses in the second month of gestation, reaches peak values around the seventh month of fetal life, declines before birth, becomes lower after parturition and finally undetectable in the adult cow. Iodothyronine 5'-deiodinase activity is present in the pericardic, peritoneal and intermuscular adipose depots of the neonatal calf, but it is always undetectable in the subcutaneous adipose tissue. It is concluded that iodothyronine 5'-deiodinase is a specific feature of brown fat in the bovine species that is not shared by white adipose tissue. white adipose tissue. Peak values of 5'-deiodinating activity appear as an early event in the prenatal differentiation programme of bovine brown-fat cells as they occur when uncoupling-protein-gene expression first starts.

Adipose Tissue, Brown↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗