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Biomedical subjects

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

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↗
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↗
PubMed1990

Purification and characterization of Escherichia coli RNase I. Comparisons with RNase M.

The endoribonuclease, RNase I, was purified from the periplasm of Escherichia coli. Based on PAGE, it has molecular mass of approximately 27 kDa with a migration rate indistinguishable from that of the recently reported RNase M from E. coli. The amino acid sequence of the two enzymes must be very similar based on two-dimensional mapping of their tryptic peptides and suggests either a post-transcriptional modification to yield different proteins from the same gene or evolution of two genes by gene duplication. However, while RNase I could degrade each of the four ribonucleotide homopolymers, only poly(U) or poly(C) were good substrates for RNase M with possibly some hydrolysis of poly(A). The reaction rate for poly(C) hydrolysis with RNase M was about ten times faster than for poly(U), while for RNase I the rates were about equal. Besides differences in specificity, RNase M was only located in the spheroplasts while RNase I found in the periplasm of growing cells. In terms of function, RNase I is known to cause degradation of rRNA during periods of stress or non-growth, whereas it has been proposed that RNase M is the endonuclease for mRNA degradation in growing cells.

Amino Acid Sequence↗
PubMed1990

Mammalian hibernation.

In mammalian hibernation, the body temperature approaches that of the surroundings, allowing large savings in energy costs of basal metabolism and eliminating the need for heat production to compensate for heat loss. During entry into hibernation, heat production ceases while the body temperature set-point gradually decreases during slow-wave sleep. In the hibernating phase, the animal copes with problems concerning the maintenance of ion gradients, possible membrane phase transitions and the risk of ventricular fibrillation. In the arousal phase, the main part of the heat and practically all the necessary substrate comes from brown adipose tissue. The hibernation season is preceded by a preparatory phase. It may be concluded that hibernation is a practical, and perhaps even enviable, solution to a mammalian problem.

Animals↗
PubMed1989

Postnatal recruitment of brown adipose tissue is induced by the cold stress experienced by the pups. An analysis of mRNA levels for thermogenin and lipoprotein lipase.

In order to investigate the postnatal recruitment process, gene expression in the brown adipose tissue of rat pups was followed during the first 20 h of life. In normal pups, the level of mRNA coding for the uncoupling protein thermogenin increased markedly but gradually within the first 24 h. Lipoprotein lipase and actin mRNA levels were relatively low and remained constant. In pups exposed to thermoneutral temperature (35 degrees C) for the first 12 h after birth, no increase in thermogenin mRNA or lipoprotein lipase mRNA was observed, whereas in pups exposed to 28 degrees C a clear increase in both thermogenin and lipoprotein lipase mRNA levels was found. Actin mRNA levels were not affected by the environmental temperature under these circumstances. It was concluded that the postnatal recruitment in brown adipose tissue is a consequence of the cold stress experienced by the newborn pups. Thus, postnatal recruitment is not ontogenically predetermined.

Actins↗
PubMed1989

Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein thermogenin: effects of hypothyroidism and norepinephrine.

Expression of the gene for the brown-fat specific uncoupling protein thermogenin was investigated in cell cultures by hybridization of isolated RNA with a cDNA clone corresponding to mouse thermogenin. The RNA was isolated 3-4 days after confluence from cells differentiated in culture from precursors isolated from the interscapular brown adipose tissue of 5-week-old mice. Very low thermogenin mRNA levels were found in cells derived from untreated mice, and there was only little effect of added norepinephrine on thermogenin gene expression in these cells. However, in cells derived from hypothyroid (methimazole-treated) mice there was a higher expression of thermogenin, and norepinephrine had a marked augmenting effect on the thermogenin mRNA level in these cells. These effects of thermogenin mRNA levels were specific, in that they contrasted with the effects of hypothyroidism and norepinephrine on the level of other mRNA species in these cells (coding for beta-actin, lipoprotein lipase, cytochrome-c oxidase, and glycerol-3-phosphate dehydrogenase). It was concluded that brown-fat cells in culture can reach a differentiated state, sufficiently advanced that the unique properties of these cells can be expressed, and that thermogenin gene expression (i.e., the level of thermogenin mRNA) is under direct control of norepinephrine.

Actins↗
PubMed1989

Effects of cholera toxin on gene expression in brown preadipocytes differentiating in culture.

To investigate the cellular control of the recruitment process in brown adipose tissue, the ability of cholera toxin to influence the differentiation of brown preadipocytes developing in culture was investigated. Stromalvascular cells obtained from the brown adipose tissue of 3-wk-old rats were grown in culture for 6-7 days in the presence or absence of cholera toxin. It was found that cholera toxin treatment decreased the expression of the actin gene (indicating an increased degree of differentiation), while at the same time promoting the expression of the genes coding for the mitochondriogenesis marker cytochrome-c oxidase and for the adipocyte conversion marker lipoprotein lipase (all followed at the mRNA level). Chronic cholera toxin treatment also increased the total amount of protein per cell in culture, and a specific cholera toxin-induced 35-kDa protein was identified. It was concluded that (in contrast to the case suggested for white preadipocytes) cholera toxin treatment of brown preadipocytes may not only affect the activity of catabolic enzymes but may also directly promote the differentiation process, indicating that this process is under beta-adrenergic control in the adapting animal.

Adipose Tissue, Brown↗
PubMed1989

Rare fatty acids in brown fat are substrates for thermogenesis during arousal from hibernation.

Because brown adipose tissue lipids are the preferred substrate for thermogenesis during arousal from hibernation, the fatty acid composition of brown fat lipids was followed during cold acclimation and during a hibernation bout. In control golden hamsters (living at 22 degrees C), the fatty acid composition of the white adipose tissue closely resembled that of the food, but brown adipose tissue contained more animal-derived fatty acids. As an effect of acclimation to cold, the fatty acid composition of brown adipose tissue changed to resemble that of the food, and no marked differences between white and brown adipose tissue were then evident. During a hibernation bout, a major part of the fatty acids accumulated in brown fat during entry into hibernation consisted of "rare" acids, such as homo-gamma-linoleic acid. Homo-gamma-linoleic, together with eicosadienoic acid and lignoceric acid, was preferentially utilized during the early phase of arousal. During this phase, "bulk" fatty acids, such as linoleic acid, were spared, whereas in late arousal, linoleic acid was the preferred substrate. It was concluded that rare fatty acids are of quantitative significance in brown adipose tissue during hibernation and arousal.

Adipose Tissue↗
PubMed1989

Effects of group therapy on parents of children with cancer.

Group therapy for parents of children with cancer has been suggested as a means of relieving stress. This quasi-experimental study sought to determine the effect of participation in a support group for parents of children aged 10 to 14 years with cancer. Parents completed the Wallston Health Locus of Control (HLOC) Scale and the Social Adjustment Scale-Self Report (SAS-SR) both before and following seven group sessions. Descriptive data were collected from the cotherapists' process log and the participants' evaluation. A significant t test score (P = .017) was obtained for the HLOC Scale questionnaire. The group process log showed recurrent themes of helplessness and powerlessness. The Parent Support Group Evaluation (PSGE) developed by the researchers, demonstrated satisfaction and revealed that school and community activities were considered the most helpful. Tentative conclusions support the value of such a group in providing a forum for the parents to discuss concerns and decrease their sense of isolation. However, more study is needed with a larger sample before definitive conclusions can be reached.

Adult↗
PubMed1988

Cold-induced beta-adrenergic recruitment of lipoprotein lipase in brown fat is due to increased transcription.

The cellular basis for the cold-induced increase in lipoprotein lipase activity in rat brown adipose tissue was investigated. Rats were treated with inhibitory agents and either exposed to cold for 4 h or injected with isoprenaline. Lipoprotein lipase activity was followed in acetone-ether extracts of the tissue. Besides cold, both the beta-adrenergic agonist isoprenaline and the adenylate cyclase activator cholera toxin were able to increase lipoprotein lipase activity in the tissue. The protein synthesis inhibitor cycloheximide fully abolished this response; the half-life of lipoprotein lipase activity was both in control and in the cold-exposed state approximately 2 h. Also the mRNA synthesis inhibitor actinomycin D fully abolished the cold-, the isoprenaline-, and the cholera toxin-induced increases in lipoprotein lipase activity; the half-life of lipoprotein lipase mRNA was estimated to be 20-30 h. However, in animals returned to control conditions after a 4-h cold stress, the decline in activity corresponded to a half-life of only 4 h. It was concluded that the increase in lipoprotein lipase activity in the brown adipose tissue of cold-exposed rats is not due to an activation of preexisting enzyme nor due to an increased half-life of functional enzyme. Rather it is suggested that in brown adipose tissue the rate of lipoprotein lipase gene transcription is positively regulated by the cellular level of cAMP and that this increase in lipoprotein lipase mRNA leads directly to an increased rate of enzyme synthesis and hence to the increase in activity.

Adipose Tissue, Brown↗