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M Desautels

Publications and source records attributed to M Desautels.

At least 37 records · Page 2Linked to original sources
PubMed1992

Characterization of norepinephrine-stimulated protein synthesis in rat brown adipocytes.

Rat brown adipocytes were incubated for 24 h with or without norepinephrine (NE) in Dulbecco's modified Eagle's medium with albumin, calf serum, and antibiotics. Brown fat cells were viable as defined by unchanged cell morphology, ATP content, or basal and NE-stimulated respiration. However, a 24-h exposure to NE led to a decline in NE-stimulated respiration that was not due to loss of thermogenic capacity. Brown fat cells incubated with or without NE had similar protein, succinate dehydrogenase, and uncoupling protein (UCP) content. These results differ from those observed after food deprivation in rats where loss of mitochondrial proteins occurs within 24 h, suggesting that reduced exposure to NE is not the only factor responsible for brown fat atrophy. NE increased [35S]methionine incorporation into cellular proteins, mitochondrial proteins, and UCP. The effect of NE on cell protein synthesis was inhibited by propranolol but not by prazosin. It was also inhibited 95% by cycloheximide but only partially (50%) by actinomycin D in contrast to NE stimulation of UCP labeling, which required RNA transcription. Chloramphenicol-sensitive protein synthesis was stimulated by NE. These results indicate a trophic action of NE in brown adipocytes exerted both at the level of RNA transcription and translation.

Adipose Tissue, Brown↗
PubMed1991

Effects of neonatal sympathectomy on brown fat development and susceptibility to high fat diet induced obesity in mice.

Injections of 6-hydroxydopamine in mouse neonates caused extensive and long lasting damage to the sympathetic nervous system and impaired brown fat development. Brown adipose tissue (BAT) thermogenic capacity of sympathectomized mice (up to 120 days old) was reduced because of marked reductions in the tissue mitochondrial protein content and the mitochondrial concentration of uncoupling protein, as assessed by [3H]GDP binding and immunoassay. Neonatal sympathectomy did not affect BAT DNA content. Sympathectomized mice also had reduced epinephrine-stimulated rates of oxygen consumption. BAT of sympathectomized mice failed to respond by increases in [3H]GDP binding to isolated mitochondria and uncoupling protein concentration when animals were offered a palatable high-fat dietary supplement that increased calorie intake of both normal and sympathectomized mice. The high-fat diet caused increases in body weight, carcass fat, and gonadal white fat pad weights in sympathectomized animals that were similar to those of control mice. These results show that inactivation of BAT metabolism did not accentuate the development of obesity caused by a dietary supplement rich in fat and suggest that stimulation of BAT metabolism was not very effective in counteracting the obesity-inducing effect of this diet.

Adipose Tissue, Brown↗
PubMed1990

Role of acid proteases in brown adipose tissue atrophy caused by fasting in mice.

The lysosomal proteolytic capacity of mouse brown adipose tissue (BAT) and its role during fasting were evaluated. The specific activities of acid phosphatase and cathepsins B, D, H, and L were measured in BAT of mice acclimated at 33, 21, and 4 degrees C and in BAT undergoing different rates of protein loss during a 24- to 48-h fast. The specific activities of lysosomal proteases in BAT did not vary with the acclimation status of the animals. Mice acclimated at 33 degrees C showed no significant atrophy of BAT after a fast. In mice kept at 21 degrees C, protein loss from BAT was observed after a fast without change in tissue DNA content. Protein loss from BAT was partially reduced by injection of the acidotropic agent chloroquine. Furthermore, tyrosine release from BAT during fasting was also reduced by injections of chloroquine or leupeptin, a thiol-protease inhibitor. Tyrosine release from BAT was maximum within 24 h and returned to prefast values by 36 h, suggesting rapid activation followed by inhibition of the tissue proteolytic activity. However, there was no change in acid protease specific activities, suggesting that these enzymes were not limiting for protein degradation. When cold-acclimated mice were fasted at 21 degrees C, BAT protein loss was markedly enhanced and increases in cathepsin D and L activities were observed, but there was no change in cathepsin B and H and acid phosphatase specific activities. These results indicate that BAT contains an important lysosomal proteolytic pathway that is involved in the rapid reduction of the tissue thermogenic capacity during a fast.

Adipose Tissue, Brown↗
PubMed1990

Role of neural input in photoperiod-induced changes in hamster brown adipose tissue.

Repeated injections of 6-hydroxydopamine in Syrian hamster neonates maintained under long-day (16L:8D) photoperiod for 30 days retarded body growth and cellular proliferation in brown adipose tissue but did not affect the cellular content of mitochondrial proteins. Sympathectomy reduced GDP binding to isolated mitochondria without affecting the organelle uncoupling protein (UCP) content. Unilateral surgical denervation of the brown fat pad of 30-day-old hamsters caused loss of tissue protein and succinate dehydrogenase as well as reductions in GDP binding and UCP content of isolated mitochondria but did not prevent an increase in GDP binding observed after 1 month exposure to a short-day photoperiod. The increased GDP binding was not due to increased UCP content. These results indicate that an adrenergic neural input may not be essential for UCP expression in Syrian hamsters and that changes in GDP binding observed in a short-day photoperiod environment can be observed in denervated tissue in the absence of changes in mitochondrial UCP content.

Adipose Tissue↗
PubMed1990

Importance of neural input and thyroid hormones in the control of brown fat atrophy in mice.

In euthyroid mice, a 48-h fast caused brown fat (BAT) atrophy characterized by loss of tissue proteins, succinate dehydrogenase (SDH), and a significant reduction in mitochondrial uncoupling protein (UCP) content. Chemical sympathectomy and surgical denervation failed to mimic the changes in BAT protein and SDH contents observed after food deprivation. However, suppression of sympathetic activity could account for the loss of UCP from the mitochondria. In mice made hyperthyroid by repeated triiodothyronine injections, losses of tissue SDH and proteins caused by food deprivation or surgical denervation were markedly suppressed, while the loss of UCP from the mitochondria remained unchanged. These results suggest that reduced sympathetic activity to BAT in fasted mice is not the exclusive cause of the tissue atrophy and that thyroid hormones may play a role in the control of brown fat atrophy in mice.

Adipose Tissue, Brown↗
PubMed1990

Weight gain and brown fat composition of mice selected for high body weight fed a high-fat diet.

Mice selected for high body weight (QL522) had increased food intake, body weight gain, and fat deposition relative to mice without weight selection (QL521). Brown adipose tissue (BAT) thermogenic capacity, as determined by the tissue content of protein, DNA, and succinate dehydrogenase and by mitochondrial uncoupling protein content was similar or slightly higher in 2- and 10-mo-old QL522 mice relative to age-matched QL521 mice. When food intake of QL522 mice was restricted to the level of QL521 mice, body weight gain and fat deposition over 28 days were then comparable to those of QL521 mice. Food restriction had no effect on BAT composition of QL522 mice. Both QL521 and QL522 mice increased calorie intake by 40-50% when offered a palatable high-fat supplement (HF), but only QL522 mice increased weight gain and fat deposition significantly. QL521 mice fed a high-fat supplement showed a significant increase in brown fat succinate dehydrogenase content, whereas QL522 mice showed significant increases in brown fat weight, protein, and succinate dehydrogenase content relative to mice fed stock diet. Nonshivering thermogenic capacity, as assessed by norepinephrine-stimulated oxygen uptake in anesthetized animals at 30 degrees C was similar between QL521 and QL522 mice eating stock diet and was significantly increased by the high-fat supplement in both strains. Thus mice selected for high body weight are very susceptible to diet-induced obesity, and we have no evidence that a reduction in brown fat thermogenic capacity contributes to the increased fat deposition of QL522 mice as they grow old or when they are offered palatable energy-dense supplements.

Adipose Tissue↗
PubMed1988

Effects of repeated cycles of fasting-refeeding on brown adipose tissue composition in mice.

Mice fasted for 24 h showed reductions in carcass fat and gonadal fat depots and atrophy of brown adipose tissue (BAT) that was characterized by loss of protein and succinate dehydrogenase. These changes were reversed on 24 h of refeeding. Cycling mice experienced 14 cycles of 1 day of fast followed by 2 days of refeeding, whereas control mice were fed ad libitum. Weight loss during each fast remained constant, and the animals lost and regained in excess of twice their initial weights within 6 wk. However, final weight and carcass and gonadal fat weights were similar to those of animals fed ad libitum. Total food intake was similar between cycling mice and those fed ad libitum suggesting an increase in feeding efficiency. There was no development of resistance to food deprivation since the preceding fasting experience of the animal had no effect on weight and carcass fat loss during a 24- or 48-h fast. Norepinephrine-stimulated oxygen consumption that was reduced in cycling mice was probably the result of a reduction of BAT thermogenic capacity. BAT succinate dehydrogenase content and the concentration of uncoupling protein in isolated mitochondria were significantly reduced. These changes in BAT composition were not observed when the refeeding period of each cycle was increased to 6 days. These results suggest that reduced energy expenditure in BAT may play a role in the conservation of energy during intermittent and frequent bouts of food deprivation.

Adipose Tissue, Brown↗
PubMed1988

Is adrenergic innervation essential for maintenance of UCP in hamster BAT mitochondria?

The importance of the neural input for the maintenance of the mitochondrial content of the uncoupling protein (UCP) in hamster brown adipose tissue (BAT) was evaluated by unilateral surgical denervation and chemical sympathectomy with 6-hydroxydopamine. These interventions alone or in combination depleted (by 90-95%) the tissue catecholamine content to the same extent. Injections of 6-hydroxydopamine to hamsters caused reductions in BAT protein content but were without significant effect on [3H]GDP binding to isolated mitochondria or on the mitochondrial content of UCP measured by immunoassay. In contrast, surgical denervation, which had much less effect on BAT composition, caused a significant loss of UCP from the mitochondria. These results differ from those obtained in rats in which both chemical sympathectomy and surgical denervation caused a loss of UCP from the mitochondria. Norepinephrine infusion (with minipumps), which prevented denervation-induced BAT atrophy and reduction in mitochondrial content of UCP in rats, caused pronounced loss of tissue mass and mitochondrial proteins in hamsters and did not prevent the loss of UCP observed in mitochondria isolated from the denervated pad. Thus an intact innervation that may not be adrenergic is required for the expression of UCP in hamster BAT mitochondria.

Acclimatization↗
PubMed1987

Selective loss of uncoupling protein mRNA in brown adipose tissue on deacclimation of cold-acclimated mice.

The time course of changes in the level of uncoupling protein mRNA when cold-acclimated mice were returned to a thermoneutral environment (33 degrees C) was examined using a cDNA probe. Upon deacclimation, there was a marked loss of uncoupling protein mRNA within 24 h, which precedes the loss of uncoupling protein from mitochondria. This loss of uncoupling protein mRNA was selective, since there was no change in the relative proportion of cytochrome c oxidase subunit IV mRNA or poly(A)+ RNA in total RNA. The results suggest that the decrease in the mitochondrial content of uncoupling protein during deacclimation is likely the result of turnover of existing protein, with very little replacement due to a lower level of its mRNA.

Acclimatization↗
PubMed1986

Unchanged nonshivering thermogenic capacity of dystrophic mice.

The rate of oxygen consumption measured at 32.5 degrees C of lightly anesthetized 129/ReJ dy/dy mice was greater than that of dy/+ or +/+ control mice. However, the norepinephrine-stimulated rates of oxygen consumption of dystrophic and normal mice were similar. Brown adipose tissue cellularity (DNA content) of dystrophic mice was unchanged, and the tissue protein and succinate dehydrogenase contents were slightly reduced. The mitochondrial concentration of the uncoupling protein, thermogenin, and purine nucleotide binding to mitochondria isolated from brown fat of normal or dystrophic mice, were similar. These results indicate that the nonshivering thermogenic capacity of dystrophic mice is not significantly altered.

Adipose Tissue, Brown↗
PubMed1986

Selective loss of uncoupling protein from mitochondria of surgically denervated brown adipose tissue of cold-acclimated mice.

The effects of unilateral surgical denervation on brown adipose tissue (BAT) composition were evaluated to assess the importance of the sympathetic innervation in the maintenance of a high concentration of the uncoupling protein thermogenin in cold-acclimated (CA) mice and to assess whether suppression of neural activity could account for BAT atrophy observed during fasting or when CA mice are returned to a thermoneutral environment (33 degrees C). Denervation-induced BAT atrophy was characterized by protein and thermogenin losses in absence of changes in the tissue cellularity (DNA content). There was a marked reduction in the concentration of thermogenin in mitochondria isolated from denervated BAT, but the concentration of the adenine nucleotide translocator was unchanged. Fasting or exposure of CA mice to 33 degrees C induced a rapid and extensive loss of tissue protein from both innervated and denervated BAT. In CA mice exposed to 33 degrees C, there was also reduction in tissue cellularity and loss of thermogenin from BAT mitochondria. Since surgical denervation suppressed BAT hyperplasia and the increase in the mitochondrial concentration of thermogenin observed during cold exposure, these results indicate that an intact innervation is required for both synthesis and maintenance of a high mitochondrial content of thermogenin in CA mice. In addition, the lesser changes in tissue composition caused by denervation compared with those caused by fasting or exposure of CA mice to 33 degrees C question the importance of the suppression of neural activity as the exclusive cause of rapid BAT atrophy in mice.

Acclimatization↗
PubMed1986

Effects of fasting and food restriction on brown adipose tissue composition in normal and dystrophic hamsters.

Fasting for 36-48 h or food restriction (30% reduction of daily food intake for 6 weeks) caused brown adipose tissue (BAT) atrophy in hamsters. Fasting-induced atrophy was characterized by reductions in tissue mass, DNA, protein, and thermogenin. By contrast, food restriction had no effect on tissue cellularity (DNA) but markedly reduced the tissue protein and thermogenin contents. The concentration of thermogenin in isolated mitochondria was unchanged by fasting or food restriction. Dystrophic hamsters had a reduced BAT mass when compared with weight-matched control hamsters. This resulted from a reduction in tissue cellularity since BAT DNA, protein and thermogenin contents were all reduced. The extent of binding of [3H]guanosine diphosphate to isolated mitochondria and their content of thermogenin were similar in normal and dystrophic hamsters. In response to cold exposure, as in normal hamsters, BAT of dystrophic hamsters grew and the tissue thermogenin increased, but the mitochondrial concentration of thermogenin did not change. In response to fasting, in contrast with normal hamsters, there was no significant reduction in BAT DNA in dystrophic animals and the loss of tissue protein was reduced. However, the relative changes in BAT composition during chronic food restriction were similar in normal and dystrophic animals. Thus, reduction in hamster BAT thermogenic capacity during food deprivation may occur by loss of cells and (or)reduction in the tissue protein and thermogenin contents. The extent of protein and (or) DNA loss may be dependent upon the original tissue mass and the severity of food deprivation.

Adipose Tissue, Brown↗
PubMed1986

Effects of cold acclimation in dystrophic hamsters: reduction of heart necrosis.

The effects of cold acclimation on brown adipose tissue, heart, and skeletal muscles were evaluated to assess if the increase in metabolic activity associated with chronic exposure to 4 degrees C had any influence on the progression of the syndrome in dystrophic hamsters. Body weight gain was much slower in dystrophic animals kept at 22 degrees C and was unaffected by cold acclimation. Rates of O2 consumption and CO2 production were similar in normal and dystrophic hamsters kept at 22 degrees C, and both were increased in cold-acclimated normal and dystrophic animals. The amount of interscapular brown adipose tissue was about one-half of normal in dystrophic hamsters kept at 22 degrees C. In response to cold acclimation, as in normal hamsters, brown adipose tissue of dystrophic hamsters grew and increased its thermogenin content by more than fourfold. However, the concentration of thermogenin in isolated mitochondria remained unchanged. Heart ventricular hypertrophy was also observed in both normal and dystrophic hamsters after cold acclimation. The number and extent of cardiac necrotic lesions were significantly reduced in cold-acclimated dystrophic animals when compared with age-matched dystrophic hamsters kept at 22 degrees C. Heart calcium content and plasma creatine kinase levels were also reduced in dystrophic hamsters after cold acclimation. However, in soleus muscles the prevalence of centronucleated fibers, an indirect cumulative index of necrosis, as well as the extent of tissue necrosis were not significantly reduced in cold-acclimated dystrophic animals. Thus cold acclimation of dystrophic hamsters appeared to reduce necrosis predominantly in the heart.

Adaptation, Physiological↗
PubMed1985

Thermoregulatory responses of dystrophic hamsters to changes in ambient temperatures.

The ability of dystrophic hamsters to maintain their body temperature despite abnormal muscle and brown adipose tissue, two organs involved in thermoregulation, was evaluated. Dystrophic hamsters (CHF 146) between the ages of 30 and 160 days kept at 21 degrees C had core (rectal) temperatures (TR) that were 0.5-1.5 degrees C lower than Golden Syrian controls. The reduced core temperatures of dystrophic hamsters were unlikely the result of an incapacity to generate heat since the dystrophic hamsters were able to maintain their TRs during 3 h of acute cold stress (4 degrees C) and to adapt to prolonged cold exposure. However, TRs of cold-acclimated dystrophic hamsters were still 1 degree C below TRs of cold-acclimated control animals. By contrast, increasing the ambient temperature raised TRs of both normal and dystrophic hamsters. When kept at 32 degrees C overnight, the TRs of dystrophic hamsters remained significantly below those of control animals. When heat-exposed dystrophic hamsters were returned to 21 degrees C, their TRs returned to values significantly lower than those of control hamsters. Thus, dystrophic hamsters showed a capacity to thermoregulate, like control hamsters, but appeared to do so at a lower temperature. The reduced core temperatures of dystrophic hamsters kept at 21 degrees C cannot be explained by a reduction in metabolic activity since newborns and 30- and 140-day-old dystrophic hamsters had rates of oxygen consumption (VO2) and carbon dioxide production (VCO2) that were similar to those of controls. These results suggest that the thermoregulatory set point may be altered in dystrophic hamsters.

Aging↗
PubMed1985

Mitochondrial thermogenin content is unchanged during atrophy of BAT of fasting mice.

The objectives of this study were to evaluate the rate at which brown adipose tissue (BAT) from mice atrophies when its thermogenic activity is suppressed during fasting or exposure to a thermoneutral environment (33 degrees C) and whether such atrophy is accompanied by loss from BAT mitochondria of "thermogenin," the GDP binding protein associated with the calorigenic proton conductance pathway. Atrophy of mouse BAT was characterized by rapid loss of protein but unchanged tissue DNA content. The rate of protein loss varied from 2 to 6 mg protein/day depending on the environmental and feeding status of the mice. In synchrony with tissue protein loss, there was a marked reduction in the tissue content of mitochondrial proteins and of thermogenin, measured by immunoassay. However, the concentration of thermogenin in isolated mitochondria was unchanged by fasting or exposure of the mice to 33 degrees C for 48 h. By contrast, marked reduction in [3H]GDP binding to isolated mitochondria were observed after exposure of the mice to 33 degrees C. Mice acclimated at 4 but not those acclimated at 21 degrees C showed reduction in GDP binding to isolated mitochondria during fasting. These results clearly indicate that changes in purine nucleotide binding to isolated mitochondria can occur in the absence of changes in the mitochondrial concentration of thermogenin. Thus rapid decrease in BAT thermogenic capacity (e.g., during fasting or 33 degrees C exposure) appears dependent on extensive loss of tissue protein, probably whole mitochondria, rather than rapid and selective removal of thermogenin from the mitochondria.

Acclimatization↗
PubMed1984

Is acute morphine hyperthermia of unrestrained rats due to selective activation of brown adipose tissue thermogenesis?

Experiments were conducted to determine if the hyperthermia after acute morphine sulfate (MS) administration was due to selective activation of brown adipose tissue (BAT) thermogenesis. Interscapular BAT temperature (TIBAT) and core (rectal) temperature (TR) were measured concurrently in groups of unrestrained, male Sprague-Dawley rats kept at 21.0 degrees C before and after i.p. (0.75, 2.0 or 10.0 mg/kg) or intracerebroventricular injections (200 ng- greater than 5 ul) of MS or sterile saline. TRS and TIBATS increased 0.6-1.0 degree C after i.p. intracerebroventricular injections of MS but the time course and magnitude of the changes in TIBATS from mean preinjections readings were not different from the increases in TRS. By contrast, isoproterenol HCl (0.5 mg/kg i.p.), known to activate BAT heat production, given to rats kept at 4 or 21 degrees C raised the TIBATS significantly above changes seen in TRS. Rats given MS in which the capacity for brown fat heat production had been increased previously (cold adaptation) or decreased (fasting or bilateral denervation) again evoked increases in TIBAT and TRS that were not significantly different from one another or from the response of warm-adapted, normophagic controls. Furthermore, oxygen uptakes were reduced after MS compared to oxygen uptakes after saline injections. [3H]Guanosine diphosphate binding to interscapular BAT mitochondria isolated from rats sacrificed at peak morphine hyperthermia (greater than 1.0 degree C) was not different from that of saline control animals. The results indicate clearly that the hyperthermia occurring in unrestrained rats after acute central or peripheral opiate administration is not due to selective activation of BAT thermogenesis.

Acclimatization↗