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B Cannon

Publications and source records attributed to B Cannon.

At least 19 recordsLinked to original sources
PubMed1995

The expression of subunit c correlates with and thus may limit the biosynthesis of the mitochondrial F0F1-ATPase in brown adipose tissue.

A low content of mitochondrial ATPase in brown adipose tissue (BAT) has previously been found to contrast with high levels of the transcripts of the beta-subunit of the F1 part of the ATPase and of the transcripts of the mitochondrial encoded subunits (Houstĕk, J., Tvrdík, P., Pavelka, S., and Baudysová, M. (1991) FEBS Lett. 294, 191-194). To delineate which subunit limits the synthesis of the ATPase complex, we have studied the expression of the nuclear genes encoding subunits alpha, beta, and gamma of the catalytic F1 part and the b, c, d, and OSCP subunits of the F0 part of the ATPase. In comparison with other tissues of mice, high levels of transcripts of alpha-F1, beta-F1, gamma-F1, b-F0, d-Fo, and OSCP were found in BAT. The only genes expressed at a low level in BAT were those of the c-F0 subunit. The levels of c-F0 transcripts were 4-70-fold lower in BAT than in other tissues. An analogous expression pattern of the ATPase genes was found in BAT of adult rat and hamster. In BAT of newborn lamb, which, in contrast to other mammals, has a high content of mitochondrial ATPase, correspondingly high levels of c-F0 mRNA were found Expression of the c-F0 genes also correlated well with the ontogenic development of BAT in the hamster, being high during the first postnatal week when mitochondria are nonthermogenic and contain a relatively high amount of ATPase, but low on subsequent days when ATPase content decreases, as the thermogenic function develops. It is suggested that expression of the c-F0 genes and subsequent synthesis of the hydrophobic subunit c of the membrane-intrinsic F0 part of the enzyme may control the biosynthesis of the ATPase complex in BAT. An analogous regulatory role of the c-F0 subunit could be postulated in other tissues.

Adipose Tissue↗
PubMed1995

Halothane selectively inhibits nonshivering thermogenesis. Possible implications for thermoregulation during anesthesia of infants.

BACKGROUND: During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia. METHODS: The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of approximately 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted. RESULTS: Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited. CONCLUSIONS: A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane-anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.

Adipose Tissue, Brown↗
PubMed1995

Polyunsaturated fatty acids recruit brown adipose tissue: increased UCP content and NST capacity.

To examine the effect of polyunsaturated fatty acids (PUFA) on brown adipose tissue recruitment and on the capacity for nonshivering thermogenesis (NST), mice were fed a diet with a standard fat content (9%) and a normal PUFA content (1.6%) (controls) or a high-PUFA content (4.3%) for 2-3 wk. The resting metabolic rate was somewhat lower in the high-PUFA group, probably due to a lower physical activity whereas the capacity for NST (estimated as the metabolic response to a norepinephrine injection) was higher in the high-PUFA group. There was no significant effect on brown adipose tissue wet weight, protein content, or cytochrome-c oxidase content, but the amount of the uncoupling protein thermogenin (UCP), measured immunologically, was significantly increased in the high-PUFA mice (totally by 41%). It was concluded that short-term feeding of a high-PUFA diet may recruit brown adipose tissue thermogenic capacity; it was speculated that earlier-reported recruiting effects of high-fat diets may not be due solely to the high total fat content of the diet but perhaps also to a specific recruiting property of the high-PUFA diets generally used in this type of investigation.

Adipose Tissue, Brown↗
PubMed1995

Cold acclimation-recruited nonshivering thermogenesis: the Syrian hamster is not an exception.

Biochemical evidence from in vitro studies of brown adipose tissue in Syrian hamsters indicates a significant degree of recruitment of the tissue as an effect of cold acclimation. However, earlier in vivo studies indicate a lack of recruitment of nonshivering thermogenesis in the intact animal as a result of cold acclimation. Because of this apparent discrepancy, the occurrence of cold acclimation-recruited nonshivering thermogenesis in hamsters was investigated. Hamsters were cold acclimated to 6 degrees C or remained at 24 degrees C (controls), and their thermogenic response was investigated in an open-circuit system at 24 degrees C. Cold acclimation resulted in a small increase in resting metabolic rate and a major increase in the thermogenic response to norepinephrine (61% increase over resting metabolic rate in controls and 156% increase in cold-acclimated animals). The absolute beta 3-specific adrenergic agonist CGP-12177 also induced a high rate of nonshivering thermogenesis, which was similarly recruited. It was concluded that, concerning the relative effect of recruitment on the capacity for nonshivering thermogenesis, the intact hamsters responded as would be predicted from in vitro experiments. Thus the hamster does not seem to constitute an exception to the general patterns described for other rodents concerning recruitment of nonshivering thermogenesis due to cold acclimation.

Acclimatization↗
PubMed1995

Chart for preparation of dilutions of alpha-adrenergic agonists for intracavernous use in treatment of priapism.

Treatment of priapism with intracavernous alpha-adrenergic agonist vasoconstrictor agents is well accepted, particularly for patients with priapism secondary to intracavernous injections of papaverine, phentolamine and/or prostaglandin E1. Although many alpha-adrenergic agonists are commercially available, phenylephrine is preferred because it has potent and selective alpha 1-adrenergic stimulatory properties, which can decrease arteriolar flow to the cavernous sinusoids, and no beta 1-stimulatory effect, which could cause arrhythmias and angina in susceptible patients. Before intracavernous injection or irrigation an alpha-adrenergic agonist must be diluted. However, no readily available reference source lists this information. Therefore, we prepared a chart for extemporaneous preparation of dilutions of alpha-adrenergic agonists for intermittent injection or irrigation.

Adrenergic alpha-Agonists↗
PubMed1994

Choline+ is a low-affinity ligand for alpha 1-adrenoceptors.

The effect of choline+, a commonly used Na+ substitute, on ligand binding to alpha 1-adrenoceptors was investigated. It was found that replacement of 25% of the Na+ in a Krebs-Ringer bicarbonate buffer with choline+ led to a 3-fold decrease in the apparent affinity of [3H]prazosin for its binding site (i.e. the alpha 1-receptor) in a membrane preparation from brown adipose tissue, while no decrease in the total number of binding sites was observed. Similar effects were seen in membrane preparations from liver and brain. In competition experiments, it was found that choline+ could inhibit [3H]prazosin binding; from the inhibition curve, an affinity (Ki) of 31 mM choline+ for the [3H]prazosin-binding site could be calculated. In fully choline(+)-substituted buffers, where the level of [3H]prazosin binding was substantially reduced, both phentolamine and norepinephrine could still compete with [3H]prazosin for its binding site, with virtually unaltered affinity; thus choline+ did not substantially affect the characteristics of those receptors to which it did not bind. Choline+ did not affect the binding characteristics of the beta 1/beta 2 radioligand [3H]CGP-12177; thus, the effect on alpha 1-receptors was not due to general, unspecific effects on the membrane preparations. It is concluded that choline+ possesses characteristics similar to those of a competitive ligand for the alpha 1-adrenoceptor; it has a low affinity but the competitive type of interaction of choline may nonetheless under experimental conditions interfere with agonist interaction with the alpha 1-receptor.

Adipose Tissue, Brown↗
PubMed1994

Stabilization of the mRNA for the uncoupling protein thermogenin by transcriptional/translational blockade and by noradrenaline in brown adipocytes differentiated in culture: a degradation factor induced by cessation of stimulation?

The stability of the mRNA coding for the uncoupling protein thermogenin was investigated in mouse brown-fat cells differentiated in culture. After 7 days in culture, the cells were stimulated for 24 h with noradrenaline, and a high level of thermogenin mRNA was then observed. If noradrenaline treatment was continued, the mRNA level remained high, but, upon withdrawal of noradrenaline, the level decreased rapidly, with a half-life of only 2.7 h. The presence of transcriptional (actinomycin) or translational (cycloheximide) inhibitors prolonged the apparent half-life by about 50%. The presence of noradrenaline during transcriptional blockade led to a further stabilization of thermogenin mRNA. It was concluded that an induced (or short-lived) gene product is important for thermogenin mRNA degradation. Direct interaction of noradrenaline with the cultured brown adipocytes could apparently not mimic the paradoxical destabilization of thermogenin mRNA in vivo, previously observed in the cold-exposed mouse [Jacobsson, Cannon and Nedergaard (1987) FEBS Lett. 244, 353-356], indicating significant differences between the systems in vitro and in vivo.

Adipocytes↗
PubMed1994

Sulfonates are low-affinity ligands for the GDP-binding site of brown-fat mitochondria.

In order to study the function of the brown-fat specific uncoupling protein thermogenin (UCP), the effect of certain sulfonates on [3H]GDP binding to the GDP-binding site of brown adipose tissue mitochondria was studied. The affinity of [3H]GDP for the site was 1.3 microM in the normal sucrose medium, but the apparent KD was increased to approximately 20 microM in 100 mM hexanesulfonate medium. This increase in apparent KD was found to be due to a competitive binding of hexanesulfonate to the GDP-binding site; the affinity of hexanesulfonate was only 13 mM but this was sufficient to affect the apparent affinity of GDP under experimental conditions. Also in KCl-medium, the affinity of GDP was high (approximately 3 microM), but both in a benzenesulfonate medium and in a para-aminobenzenesulfonate (sulfanilate) medium, the apparent affinity was lower (approximately 12 microM); as benzenesulfonate is well transported by thermogenin but sulfanilate is not, the reduction in affinity was unrelated to transport. In agreement with earlier data (Jezek, P. and Garlid, K.D. (1990) J. Biol. Chem. 265, 19303-19311), the potency of GDP to inhibit transport was dependent on the species transported; the fact that GDP potency was lower for benzenesulfonate transport (EC50 = 324 microM) than for Cl- transport (EC50 = 32 microM) could adequately be explained by the competitive interaction of benzenesulfonate with the GDP-binding site, but this effect could only partly explain the even lower potency of GDP to inhibit hexanesulfonate transport (EC50 = 4074 microM). It was concluded that these types of substrate for thermogenin-mediated transport may directly interact with the GDP-binding site, but that this effect could only partly explain the dependence of GDP potency on substrate species.

Adipose Tissue, Brown↗
PubMed1994

Thermogenesis in brown adipocytes is inhibited by volatile anesthetic agents. A factor contributing to hypothermia in infants?

BACKGROUND: In infants, nonshivering thermogenesis from brown adipose tissue provides an important source of heat for thermoregulation. Infants are known to have a high susceptibility to hypothermia during anesthesia. To investigate whether this could be due to an inhibition of nonshivering thermogenesis by anesthetics, the effect of preincubation with volatile anesthetics on the norepinephrine-induced heat production of brown adipocytes was investigated. METHODS: Brown adipocytes from hamsters were isolated with a collagenase digestion method and preincubated with volatile anesthetics. The cells were stimulated with norepinephrine, and heat production, measured as oxygen consumption, was monitored polarographically. RESULTS: Norepinephrine addition led to a 20-fold increase in the rate of oxygen consumption (thermogenesis). However, preincubation of cells with 3% halothane reduced the response to norepinephrine by more than 70%. The potency of norepinephrine (the median effective concentration) was not affected by halothane. Full effect of halothane was reached quickly, and after halothane withdrawal, the thermogenic response recovered, although rather slowly. Halothane, isoflurane, and enflurane were approximately equipotent inhibitors of thermogenesis, with concentrations of approximately 0.7% resulting in 50% inhibition. The inhibitory effect of 1% halothane was unaffected by the presence of 74% nitrous oxide, but nitrous oxide alone also reduced thermogenesis. CONCLUSIONS: Volatile anesthetics severely attenuated the thermogenic response to norepinephrine of isolated brown-fat cells. It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. Because infants are dependent on brown-fat-derived nonshivering thermogenesis for thermal balance, the inhibition by volatile anesthetic agents of brown-adipocyte heat production may at least partly explain the susceptibility of infants to hypothermia during and after anesthesia.

Adipocytes↗
PubMed1994

Coexisting beta-adrenoceptor subtypes: significance for thermogenic process in brown fat cells.

The possible significance of the coexisting beta 1-, beta 2-, and beta 3-adrenoceptors in brown adipose tissue for the thermogenic response was investigated. Oxygen consumption of isolated hamster brown fat cells was analyzed as a measure of thermogenesis. Thermogenesis could be evoked not only by the physiological agent norepinephrine but also by BRL-37344 and CGP-12177. No evidence for biphasic inhibition curves was found with either the selective beta 1-antagonist ICI-89406, the beta 2-antagonist ICI-118551, or the beta 1/beta 2-nonselective beta-antagonist propranolol against 1 microM norepinephrine; pI50 (the negative logarithm of the inhibitory constant for an antagonist, as estimated from the dose-response curve for an antagonist vs. a constant agonist concentration) values for ICI-89406 and ICI-118551 were very low (4-5), implying nonselective inhibition; the pI50 for propranolol was approximately 6 (as expected for the beta 3-receptor). Even with suboptimal norepinephrine, no biphasic inhibition was found. CGP-12177 at concentrations where it is primarily an antagonist to the beta 1-receptor did not influence the dose-response curve for either norepinephrine or BRL-37344. BRL-37344- or CGP-12177-induced thermogenesis was inhibited by the beta-antagonists in a manner similar to norepinephrine-induced thermogenesis. Schild plots for propranolol inhibition of norepinephrine-, isoprenaline-, BRL-37344- and CGP-12177-induced thermogenesis yielded similar pA2 (the negative logarithm of the inhibitory constant for an antagonist, as calculated from a series of agonist dose-response curves at different antagonist concentrations) (approximately 5.5), for interaction with either agonist, implying that the same receptor was stimulated by all agonists. Thus, despite the fact that different beta-receptor subtypes coexist in the tissue, we find no evidence for the participation of beta 1- or beta 2-receptors in the thermogenic response. Within the resolution of the experiments, the results therefore imply that it is predominantly or solely the beta 3-receptor that is coupled to thermogenesis, and it is via this beta-adrenergic receptor that not only norepinephrine but also CGP-12177 and BRL-37344 induce thermogenesis.

Adipose Tissue, Brown↗
PubMed1994

The uncoupling protein thermogenin during acclimation: indications for pretranslational control.

To analyze the regulation of the content of the uncoupling protein thermogenin in brown adipose tissue, we have selected a physiological transition phase during which to investigate the relationship between the level of mRNA and the level of the ensuing protein product. Mice preacclimated to 28 degrees C were transferred to 4 degrees C. Cold acclimation led to the expected increases in brown fat total protein and RNA content. Two recruited proteins were analyzed: the cytosolic glycerol-3-phosphate dehydrogenase and the mitochondrial uncoupling protein thermogenin. The activity of the dehydrogenase acutely followed the level of the corresponding mRNA, indicating pretranslational control. However, for thermogenin there was a marked time delay between the establishment of the fully recruited level of thermogenin mRNA (after only approximately 4 h of cold exposure) and that of thermogenin itself (after > 3 wk). By reiterative computer simulation, it was investigated whether a model only involving pretranslational regulation could be invoked for either system. For glycerol-phosphate dehydrogenase, a plausible model could be constructed, provided the protein half-life was shorter than approximately 24 h. Despite the long time delay between full thermogenin mRNA recruitment and full thermogenin protein recruitment, a plausible pretranslational control model could also be constructed, provided that the protein half-life was approximately 5 days. This computed value was in good agreement with the half-life obtained from independent thermogenin half-life studies. It is implied that pretranslational control may suffice to explain the regulation of thermogenin content in brown adipose tissue during a warm-to-cold transition period.

Acclimatization↗
PubMed1993

Attenuation of Gs alpha coupling efficiency in brown-adipose-tissue plasma membranes from cold-acclimated hamsters.

In order to localize site(s) of beta-adrenergic desensitization found in brown adipocytes from cold-acclimated animals, total brown-adipose-tissue homogenates (postnuclear supernatant) were obtained from control or cold-acclimated hamsters and were fractionated on discontinuous sucrose gradients. A low-density band (cytosolic proteins) and a high-density band (mitochondria) were obtained; in the middle fractions only low levels of protein were recovered. However, these fractions displayed a high level of specific [3H]ouabain binding, indicating that they represented fractions enriched in plasma membranes. The level of [3H]ouabain binding was significantly higher in plasma membranes from cold-acclimated animals, indicating an increased density of Na,K-ATPase units. The maximal activity of adenylate cyclase, as estimated with forskolin, was not changed by cold acclimation. However, the levels of cyclase activity observed after Gs-protein-mediated activation (with guanosine 5'-[gamma-thio]triphosphate, isoprenaline, both of these, or fluoride) were decreased, indicating a decreased coupling efficiency. Notably, a significant decrease was observed in the functional activity of the Gs protein, as directly measured by estimation of the ability of cholate extracts of brown-fat plasma membranes to reconstitute Gs-protein-mediated stimulation of adenylate cyclase in cyc- membranes. Further, a functionally significant decrease (to 72%) was observed in the ratio between the amount of functional Gs proteins and adenylate cyclase units. The total content of Gs alpha protein was decreased to the same extent as the coupling efficiency of the membranes, indicating that a lower content of functionally equivalent Gs alpha molecules could explain the decreased coupling. It could therefore be concluded that a decrease in Gs-protein-mediated coupling efficiency, owing to a decrease in the amount of Gs alpha, is at least one site of beta-adrenergic desensitization in cold-acclimated animals. This may, at least in part, explain that desensitization takes place despite the fact that the beta 3-adrenoceptor itself apparently lacks some of the sites known to be involved in the desensitization process in other beta-adrenergic receptors.

Acclimatization↗
PubMed1992

Induction and degradation of the uncoupling protein thermogenin in brown adipocytes in vitro and in vivo. Evidence for a rapidly degradable pool.

The induction and degradation of the brown-fat-specific uncoupling protein thermogenin in brown fat cell cultures was investigated. Cultures were initiated with undifferentiated precursor cells from young mice and the amount of thermogenin was determined by immunoblotting. High levels of thermogenin could be induced by noradrenaline treatment in cells grown for more than 5 days in culture, and in such cell cultures continuously stimulated with noradrenaline, the thermogenin level continued to increase for at least a further 5 days. In cell cultures stimulated for only 24 h, the induced thermogenin was subsequently specifically and rapidly degraded, with a half-life of 20 h. As the half-life was prolonged by cycloheximide treatment, the degradation was apparently due to the induction of specific proteins after cessation of adrenergic stimulation. In cell cultures continuously stimulated with noradrenaline for 5 days, the induced thermogenin was degraded much more slowly after noradrenaline removal, with a half-life of 70 h. This half-life was unchanged by cycloheximide treatment, and the degradation after cycloheximide was in parallel with the degradation of protein in general, and was therefore non-specific. The prolongation of the half-life of thermogenin after the chronic treatment may be related to mitochondrial incorporation of thermogenin and consequent stabilization of the protein. The half-life of thermogenin in an in vivo situation of similar experimental design (the reacclimation of mice to warm after 5 days in the cold), was also long (about 7 days), and the loss was also non-specific, as it paralleled the loss of protein. Thus different molecular events are involved in thermogenin degradation when the protein is found in different functional pools.

Adaptation, Physiological↗
PubMed1992

Regulation of expression of the lipoprotein lipase gene in brown adipose tissue.

The regulation of lipoprotein lipase gene expression in brown adipose tissue was studied. Rats were preacclimated to 21 degrees C. Exposure to cold (4 degrees C) resulted in a rapid increase in the level of lipoprotein lipase mRNA in the tissue. The level peaked (expressed per microgram total RNA) after approximately 8 h and then slowly declined. The increased lipoprotein lipase mRNA level was not due to an increased stability of the mRNA, but, in a transition event from a high to a low expression of the lipoprotein lipase gene, a transcription-dependent process was recruited that accelerated the breakdown of lipoprotein lipase mRNA. Norepinephrine injections increased lipoprotein lipase mRNA levels in the tissue; this effect was mediated via a beta-adrenergic receptor. The effect of cold could be mimicked by norepinephrine injections, and these two effects were not additive, indicating that the cold effect was mediated by norepinephrine. The lipoprotein lipase mRNA level was also increased by insulin injections (into fasted animals); thus an increase in lipoprotein lipase gene expression in brown adipose tissue may be induced via two different stimuli, which, intracellularly, would be mediated via different signaling systems. In all investigated conditions, the changes in lipoprotein lipase mRNA levels observed here were parallelled by alterations in lipoprotein lipase activity reported earlier from this laboratory. It was therefore concluded that, under the conditions studied, lipoprotein lipase activity in brown adipose tissue was primarily regulated at the transcriptional level.

Adipose Tissue, Brown↗
PubMed1992

Increased alpha 1-adrenoceptor density in brown adipose tissue indicates recruitment drive in hypothyroid rats.

The effects of hypothyroidism on whole body thermogenesis, brown adipose tissue recruitment state, and alpha 1-adrenergic receptor density were investigated. Treatment of rats with methimazole for 4-5 wk led, as expected, to reduction of growth and resting metabolic rate. The thermogenic response to norepinephrine injection was practically abolished. Generally, only small effects of hypothyroidism on brown adipose tissue were observed: total protein content, mitochondrial GDP binding capacity, and total content of the uncoupling protein thermogenin were not altered. The density of beta-adrenergic receptors (estimated with [3H]CGP-12177 as a ligand) was also unchanged. However, the density of alpha 1-adrenergic receptors (estimated with [3H]prazosin) was markedly increased; in other physiological conditions, such an increase has been associated with an increased degree of recruitment of the tissue. These data indicate that brown adipose tissue in the subthermoneutral hypothyroid animal, probably due to homeostatic mechanisms, is exposed to an increased sympathetic stimulation, leading to an increased alpha 1-adrenoceptor density. However, other features of recruitment are only poorly induced, probably due to attenuation of the beta-adrenergic signaling mechanism. The increased alpha 1-adrenergic receptor density may be responsible for certain altered features of brown adipose tissue in hypothyroid animals, such as peroxisomal recruitment and perhaps also for maintenance of the thermogenin content. The results also indicate that the increased alpha 1-adrenergic density generally seen in recruitment would not result from chronic beta-adrenergic stimulation of the tissue but may be controlled via another regulatory pathway, e.g., via the alpha 1-adrenergic pathway itself.

Adipose Tissue, Brown↗
PubMed1990

Alpha- and beta-adrenergic induction of the expression of the uncoupling protein thermogenin in brown adipocytes differentiated in culture.

In order to examine the control of expression of the gene coding for the brown fat specific uncoupling protein thermogenin (UCP), brown fat cells isolated as undifferentiated precursors from the interscapular brown adipose tissue of young mice were grown in culture. In these cells, it was possible by norepinephrine (NE) addition to induce specifically the expression of the UCP gene. The effect of NE was due to activation of transcription. The ability to express the UCP gene was maximal in cells around confluence; cell cultures younger or older than this showed a lower response. The response to NE showed a sharp optimum around 0.1 microM and was linear with time over the 4-h period studied. The presence of insulin or thyroid hormones facilitated the NE response. Pharmacological analysis of the adrenergic response indicated that UCP gene expression could be induced both via beta-receptors (probably beta 3) and via alpha 1-receptors; these effects were synergistic. It was concluded that it is possible to promote these precursor cells to advance to such a state of differentiation that they can demonstrate the selective feature of the brown fat cell, i.e. the ability to express UCP. The expression of the UCP gene is regulated via interacting adrenergic mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Norepinephrine-induced synthesis of the uncoupling protein thermogenin (UCP) and its mitochondrial targeting in brown adipocytes differentiated in culture.

Synthesis of the brown adipocyte-specific mitochondrial uncoupling protein thermogenin (UCP) is demonstrated here in brown adipocytes differentiated in culture from precursor cells. By immunoblotting, no UCP was detectable in untreated multilocular adipocytes. The synthesis of UCP was stimulated by norepinephrine at physiological concentrations and was observable already after 2 h. It was evident from immunoelectron microscopy that the newly synthesised protein was targeted to the mitochondrial inner membrane, demonstrating the functional competence of these cultured cells.

Adipose Tissue, Brown↗