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J Nedergaard

Publications and source records attributed to J Nedergaard.

At least 127 records · Page 7Linked to original sources
PubMed1984

Beta-adrenergic stimulation of lipoprotein lipase in rat brown adipose tissue during acclimation to cold.

Lipoprotein lipase activity in adult rats was investigated in animals subjected to cold and to different hormonal treatments. In contrast to changes in tissue wet weight and total protein content, which showed a lag time of about 1 day, lipoprotein lipase activity was markedly (fourfold) increased after only 4 h in the cold. Total lipoprotein lipase activity reached a plateau already after 1-3 days, whereas wet weight and protein content did not plateau until 3 wk. Neither insulin nor glucose injections could mimic the cold-induced increase in lipoprotein lipase activity seen after 4 h. However, the effect of norepinephrine injections was identical to the effect of cold. The beta-agonist isoprenaline was as effective as norepinephrine, whereas the alpha-agonist phenylephrine had no effect. The beta-antagonist propranolol inhibited the cold-induced increase in lipoprotein lipase activity. It is concluded that, in contrast to white adipose tissue, brown adipose tissue lipoprotein lipase is stimulated in vivo by a beta-adrenergic mechanism and that it is this beta-adrenergic mechanism that is responsible for the rapid recruitment of lipoprotein lipase during cold exposure.

Adipose Tissue, Brown↗
PubMed1984

Preferential utilization of brown adipose tissue lipids during arousal from hibernation in hamsters.

The participation of brown adipose tissue in the arousal process of golden hamsters was studied. The utilization of lipids in different depots of brown adipose tissue was followed gravimetrically. From both the interscapular and the cervical brown adipose tissue depots, 28 mg of lipid were lost during arousal; there was no measurable loss of lipid from the white adipose tissue depots. The total weight of eight identified depots of brown adipose tissue in nonhibernating, cold-acclimated hamsters was estimated to be 1,700 mg, of which 475 g were lipid. It is calculated that a total of 255 mg lipid disappeared from brown adipose tissue during arousal; this lipid is theoretically capable of giving rise to 2.4 kcal (9.9 kJ) of heat. It is concluded that the heat produced by the combustion of the lipid that disappeared from the brown adipose tissue during the arousal process could be the major source of the heat needed to rewarm the hamster from hibernating to euthermic body temperatures.

Adipose Tissue↗
PubMed1983

Quantitative differentiation of alpha- and beta-adrenergic respiratory responses in isolated hamster brown fat cells: evidence for the presence of an alpha 1-adrenergic component.

The respiratory (thermogenic response of brown fat cells has been investigated for differentiation between alpha- and beta-adrenergic components. The relative sensitivity of the cells generally followed the pattern of the EC50 for isoprenaline less than norepinephrine = epinephrine much less than phenylephrine and the response to all these agonists was much more sensitive to propranolol than to phentolamine. Based on these criteria the response was primarily beta 1. However, the biphasic nature of the dose-response curves and the antagonist inhibition curves indicated additionally the presence of an alpha-component. Inhibition studies demonstrated the IC50 series: prazosin less than phentolamine less than yohimbine, indicating that the alpha-component is of the alpha 1-subtype. The effects of selective alpha- and beta-stimulation were additive. The maximal oxygen consumption of isolated hamster brown fat cells was composed of an 80% beta 1 adrenergic component and a 20% alpha 1 adrenergic component. Different mechanisms (beta 1 through cyclic AMP and alpha 1 possibly through Ca2+) and perhaps different purposes (e.g. short-term and long-term regulation, respectively) may explain the coexistence of two stimulatory adrenergic responses in one cell type.

Adipose Tissue, Brown↗
PubMed1983

The relationship between extramitochondrial Ca2+ concentration, respiratory rate, and membrane potential in mitochondria from brown adipose tissue of the rat.

The ability of isolated mitochondria from rat brown-adipose tissue to regulate extramitochondrial Ca2+ (measured by arsenazo) was studied in relation to their ability to produce heat (measured polarographically). The energetic state of the mitochondria was expressed as a membrane potential, delta psi (estimated with safranine), and was varied semi-physiologically by the use of different GDP concentrations. In these mitochondria GDP binds to the 32-kDa polypeptide, thermogenin, which regulates coupling. Ca2+ uptake (at 5 microM extramitochondrial Ca2+) was maximal at delta psi greater than 150 mV. Basal Ca2+ release increased from 1 to 2 nmol x min-1 x mg-1 below 150 mV. Na+ -stimulated rate of Ca2+ release was stable within the investigated delta psi span (100-160 mV). Initial Ca2+ levels were maintained below 0.2 microM for 100 mV less than delta psi less than 160 mV. Ca2+ levels maintained after Ca2+ challenge (20 nmol Ca2+ x mg-1) were below 0.4 microM for delta psi greater than 135 mM. Respiration was unstimulated for delta psi greater than 150 mV and was maximal at delta psi less than or equal to 135 mV. In the presence of well-oxidised substrates, the respiration at maximally activated thermogenin was markedly below fully uncoupled respiration and was probably limited by thermogenin activity--i.e. by a limited H+ reentry (OH- exit) and therefore by a membrane potential maintained at about 135 mV. It is concluded that at membrane potentials of 135 mV and above the mitochondria exhibit full Ca2+ control and are able to regulate thermogenic output up to maximum without interfering with this Ca2+ control. Membrane potential probably does not decrease below 135 mV in vivo. Therefore, Ca2+ homeostasis and thermogenesis are non-interfering and can be hormonally independently regulated, e.g. by alpha-adrenergic and beta-adrenergic stimuli, respectively.

Adipose Tissue, Brown↗
PubMed1983

Development of brown fat cells in monolayer culture. I. Morphological and biochemical distinction from white fat cells in culture.

The ability of cells from the stromal-vascular fraction of rat brown adipose tissue to develop into adipocytes in primary cell cultures was investigated. Comparison was made with precursor cells isolated by the same procedure from the white adipose tissue of the same animals and cultured in parallel under identical conditions. The culture procedure used allowed the cells isolated from both tissues to rapidly proliferate and differentiate. During the first week in culture the brown fat cells grew to confluence and accumulated fat in a multilocular way. During the second week, further fat was accumulated, but the cells remained multilocular. Analysis of the parallel white fat cell cultures revealed clear differences between the two adipocyte types, although the rates of cell growth were identical. Measurement of the size of the cellular lipid inclusions as a function of the time in culture indicated a much higher number of fat droplets larger than 30 micron in the white adipocytes. Moreover, after isolation of pelleting fractions of both cultured cell types, comparative functional analysis of their mitochondria by oxygen consumption measurement, as well as direct cytochrome-c-oxidase determinations, showed a significantly higher amount of mitochondria in the brown fat cell fractions than in the white fat cell fractions. It was concluded that mature brown fat contains precursor cells which can proliferate and develop into adipocytes in monolayer cell culture and which have inherent characteristics distinct from those of white fat precursor cells.

Adipose Tissue↗
PubMed1983

Effects of dietary essential fatty acids on active thermogenin content in rat brown adipose tissue.

Rats were fed diets providing either 0.3% (low EFA), 3% (control) or 10% (high EFA) of the energy as essential fatty acids. (All diets provided 20 energy percent of fat.) Both the experimental groups had a lower body weight than the controls. Small differences were found between the groups in many traditional parameters of brown adipose tissue activity (wet weight, protein content, mitochondrial content, cytochrome c oxidase activity). A specific increase in the mitochondrial concentration of the 32,000-dalton GDP-binding protein thermogenin was observed in the high EFA group (from 0.30 to 0.45 nmol/mg). When the thermogenin content of the animal was expressed per gram body weight, the content was more than doubled (from 22 to 47 pmol/g body weight) in the high EFA group, but was unaltered in the low EFA group. It is concluded that the effect of low EFA is nonspecific and due to a general decrease in health status. The effects of high EFA are, however, specific and resemble the changes observed in animals exhibiting diet-induced thermogenesis. It is suggested that the animals fed high amounts of essential fatty acids are in a state of decreased metabolic efficiency and this may be at least in part an explanation for their low body weight.

Adipose Tissue, Brown↗
PubMed1982

Exclusive occurrence of thermogenin antigen in brown adipose tissue.

Thermogenin is the purine-nucleotide binding polypeptide in brown adipose tissue mitochondria (Mr 32 000) which confers upon these mitochondria the ability to produce heat. An enzyme-linked immunosorbent assay (ELISA) has been developed to demonstrate and quantitate the occurrence of thermogenin antigen in small amounts of tissue, and thus to characterize different depots of fat tissue as white or brown. The extreme sensitivity of the method allows determination of thermogenin in samples equivalent to less than 1 mg tissue. The results indicate that thermogenin seems to be exclusively localised in brown fat mitochondria (as compared to white fat, liver or heart muscle mitochondria), and thermogenin antigen could only be found in brown adipocytes (as compared to white adipocytes). Thus, brown and white adipose tissue are probably ontogenetically different.

Adipose Tissue↗
PubMed1982

The brown fat cell.

Explore the source record for details and available documents.

Acetyl Coenzyme A↗
PubMed1982

Catecholamine sensitivity in brown fat cells from cold-acclimated hamsters and rats.

Brown fat cells, freshly isolated from cold-acclimated hamsters and rats, did not respond to norepinephrine addition with the characteristic increase in oxygen consumption (heat production) seen in cells from control animals. However, incubation of these cells for 1 h in a Krebs-Ringer bicarbonate buffer, in the presence of 10 mM pyruvate, fully restored norepinephrine responsiveness. Cells treated in this way from cold-acclimated hamsters (a hibernator) increased the rate of oxygen consumption after maximal norepinephrine stimulation as much as cells from control hamsters; also norepinephrine-stimulated fatty acid release was unaltered, indicating that brown fat cells may partly be responsible for the increase in serum fatty acid level seen during arousal from hibernation. Similarly, preincubated cells from cold-acclimated rats (a nonhibernator) increased oxygen consumption and fatty acid release as much as cells from control rats; this suggests that also in cold-acclimated rats brown fat may supply the circulation with fatty acids during cold stress. Cells from cold-acclimated animals were, however, about 10 times less sensitive to norepinephrine than cells from control animals; this desensitization may be the result of a stimulated phosphodiesterase.

Adaptation, Physiological↗
PubMed1980

Cold adaptation in the rat: increased brown fat peroxisomal beta-oxidation relative to maximal mitochondrial oxidative capacity.

Brown fat hypertrophy in the rat resulting from cold adaptation is shown here to involve increased mitochondrial, peroxisomal, and lysosomal enzyme activities. Mitochondrial activity in homogenates of brown fat was estimated as cytochrome c oxidase. After 4 wk in the cold (+5 C), the total activity was 3-fold higher than in control rats, although the specific activity was somewhat lower. Peroxisomal activity was followed as cyanide-insensitive palmitoyl-CoA-dependent NAD+ reduction (palmitoyl-CoA oxidase) and as catalase. The total activity of both palmitoyl-CoA oxidase and catalase was more than 10-fold higher than in controls and the specific activity about 3-fold higher. Acid phosphatase, used as a lysosomal marker, showed a 6-fold higher total activity and almost twice as high specific activity. The relatively greater increase in peroxisomes and lysosomes compared with mitochondria indicates an involvement in thermogenesis also for these organelles.

Acid Phosphatase↗
PubMed1979

Norepinephrine-stimulated fatty-acid release and oxygen consumption in isolated hamster brown-fat cells. Influence of buffers, albumin, insulin and mitochondrial inhibitors.

Brown fat cells isolated from adult golden hamsters have earlier been found to respond to addition of the physiological agonist norepinephrine with an increased rate of oxygen consumption and with fatty acid release. Working with these cells, we found the following. 1. The presence of albumin in the incubation medium (phosphate buffer) increases norepinephrine-induced fatty acid release and tends to stabilize the rate of oxygen consumption; bubbling of phosphate buffer with 5% CO2 in air has only a slight effect on fatty acid release. 2. In the presence of albumin, the norepinephrine-induced rate of oxygen consumption is also stable in bicarbonate buffer; it is higher than in the phosphate + CO2 buffer and the brown fat cells have a higher sensitivity to norepinephrine. 3. 20 mM phosphate (as e.g. present in a phosphate buffer) inhibits both fatty acid release and oxygen consumption. 4. Insulin inhibits the rate of oxygen consumption, but only at suboptimal concentrations of norepinephrine. 5. Atractylate inhibits submaximal norepinephrine-induced respiration, indicating that some oxidative phosphorylation takes place in norepinephrine-stimulated brown fat cells. 6. Fatty acid export from brown fat should be regarded as physiologically important.

Adipose Tissue, Brown↗
PubMed1979

Sodium-induced calcium release from mitochondria in brown adipose tissue.

Coupled mitochondria of brown adipose tissue can accumulate Ca2+ if a substrate is present. The Ca2+ is released by addition of 20 mM Na+, but not by addition of K+ or choline +. Energy-dissipating Na+-induced Ca2+ cycling occurs maximally with 20 mM Na+ and 10 microM Ca2+. In brown adipocytes, the Ca2+ ionophore A23187 and the Na+ ionophore monensin increase respiration if substrate is added, and incubation in a low-Na+ buffer decreases norepinephrine-induced respiration. Thus Na+-induced Ca2+ release takes place in brown adipose tissue; released Ca2+ could have a regulatory or thermogenic role or both.

Adipose Tissue, Brown↗
PubMed1979

The physiological role of pyruvate carboxylation in hamster brown adipose tissue.

1. Pyruvate carboxylase is present in brown adipose tissue mitochondria. 2. In isolated mitochondria, pyruvate, bicarbonate and ATP, the substrates for pyruvate carboxylase, are able to replace added malate in supplying a condensing partner for acetyl-CoA formed from beta-oxidation of fatty acids. 3. In brown adipocytes, pyruvate and CO2 increase the rate of norepinephrine-stimulated respiration synergistically. 4. The norepinephrine-stimulated respiration in brown adipocytes is diminished when pyruvate transport into the mitochondria is inhibited. 5. Pyruvate carboxylation increases the intramitochondrial level of citric acid cycle intermediates, as shown by titrations of malonate inhibition of respiration. 6. Pyruvate carboxylation can continuously supply the mitochondria with citric acid cycle intermediates, as evidenced by its ability to maintain respiration when oxoglutarate conversion to glutamate is stimulated. 7. Pyruvate carboxylation is necessary for maximal oxygen consumption even when drainage of the citric acid cycle for amino acid synthesis is eliminated. 8. Pyruvate carboxylation explains observed effects of CO2 on respiration in brown adipocytes, and may also explain the increased glucose uptake by brown adipose tissue during thermogenesis in vivo.

Adipose Tissue, Brown↗