Search PubMed⌕ Search

Biomedical subjects

J Seydoux

Publications and source records attributed to J Seydoux.

At least 55 records · Page 3Linked to original sources
PubMed1995

Dissociation of enhanced efficiency of fat deposition during weight recovery from sympathetic control of thermogenesis.

Studies reported here examined the extent to which conditions known to suppress or markedly increase the sympathetic control of thermogenesis influence enhanced efficiency of fat deposition during weight recovery after caloric restriction. To this end, measurements of energy balance and changes in body energy compartments during refeeding of rats pair fed with weight-matched controls were conducted over a 2-wk period at 22 degrees C, at thermoneutrality (29 degrees C), or in the cold (6 degrees C). The results indicate that, despite identical (or slightly lower) energy intake relative to the respective controls, the refed animals showed greater gain in body fat (by 2- to 2.5-fold), 10-12% lower energy expenditure, and higher energetic efficiency (60-80%) than the controls at all three environmental temperatures. In contrast, protein gain was not different between the refed and control groups. Thus the energy-conserving mechanism specific to acceleration of fat deposition during weight recovery persists when sympathetically driven thermogenesis is shifted from very low to very high intensity. These findings raise the possibility that this energy-conserving mechanism during refeeding may be distinct from sympathetic-dependent mechanisms underlying adaptive reduction in thermogenesis during severe energy deficit and weight loss.

Adipose Tissue↗
PubMed1994

Paraxanthine (metabolite of caffeine) mimics caffeine's interaction with sympathetic control of thermogenesis.

The notion that paraxanthine (the major dimethylated by-product of caffeine) may be a biologically active metabolite that could mediate some of the effects of caffeine was tested in relation to the well-established property of caffeine as a thermogenic stimulant. From studies measuring the in vitro respiration rates of rat brown adipose tissue in the basal state and in response to ephedrine (an enhancer of norepinephrine release from sympathetic nerve endings), it is shown that paraxanthine has the same potency as its parent compound, caffeine, in interacting with the adrenergic system to potentiate thermogenesis. These data provide the first direct demonstration of a physiological effect of the main metabolite of caffeine and raise the possibility that paraxanthine may contribute importantly to the ability of caffeine to potentiate the thermogenic effects of well-known stimuli of the sympathetic nervous system such as cold exposure, moderate exercise, and sympathomimetic drugs.

Adipose Tissue, Brown↗
PubMed1993

Real-time measurement of the contribution of the muscular activity to the metabolic rate in freely moving rats.

A new real-time ergometric system, ERGORAT, for measuring the energy expenditure due to muscular activity of small mammals is described. The method is based on measuring the vibrations induced by a freely moving rat to a platform on which it is living. Six accelerometers placed on the platform detect all the vibrations produced by the rat. The co-ordinates of the centre of mass of the animal are located by an optoelectronic device. This location and the six accelerations are fed to a microprocessor-based data acquisition and processing system. Using a Lagrangian dynamic model, the values of the mechanical energy transferred to the platform are computed every second. ERGORAT is used as part of an experimental setup allowing the measurement of the energetic balance of lean and obese rats. The results clearly show that the increase in metabolic rate of obese rats during cold exposure can be entirely explained by the cost of their increase in locomotor activity, whereas for lean rats, this cost accounts for only 41.5 per cent of their metabolic increase, the remaining being the contribution of their active brown adipose tissue.

Animals↗
PubMed1992

Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition?

Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate.

Adenosine↗
PubMed1992

The comparative test performance of dot filter hybridization (Viratype) and conventional morphologic analysis to detect human papillomavirus.

To investigate the test performance of a commercially available detection kit for human papillomavirus (HPV), the relationship between the detection of HPV by dot filter hybridization (DFH) and by standard morphologic methods was studied. Four hundred two cervical samples taken from 381 patients referred to a colposcopy clinic were examined. Human papillomavirus DNA sequences were identified and typed using commercially available anti-sense RNA probes. Simultaneous cytologic smears were obtained in 289 patients, directed biopsy samples in 284, and both smears and biopsy samples in 171 samples. Human papillomavirus DNA was detected in 164 specimens (41%), of which 24 (15%) were type 6/11, 74 (45%) were type 16/18, 39 (24%) were type 31/33/35, and 27 (16%) were untyped due to the presence of multiple positive signals. Viral types 16/18 and 31/33/35 were eight and six times more frequent in cervical intraepithelial neoplasia (CIN) II/CIN III lesions than in condyloma/CIN I, respectively. When the cytologic diagnosis was considered the standard of reference, the results of DFH for the detection of HPV were concordant in 167 (56%) paired samples. The sensitivity of DFH was 48% and the specificity was 77%. The distribution of the morphologic diagnoses in the group of false-negative results and true-positive results was similar. When the histologic diagnosis was considered the standard of reference, the efficiency of DFH was 62%, the sensitivity was 59%, and the specificity was 79%. In the subgroup of 118 samples with simultaneous smear and biopsy and at least one positive examination, 42 (36%) were positive by all three methods, 42 (36%) by two, and 34 (29%) by one, including 6 (5%) by DFH alone. Fifteen cases more were detected by the complementary use of DFH and cytology than with cytology alone. The results demonstrated that the sets of patients positive for HPV when detected by DFH or by morphologic methods were not identical but rather overlapped. The detection of HPV may be slightly improved by using DFH in addition to conventional examinations. A significant number of HPV-positive patients without a morphologic lesion and patients with low-grade lesions had HPV 16/18 or 31/33/35, suggesting a possible role for typing in establishing a risk profile. However, given uncertainties in understanding the biology of HPV-associated lesions, the role, if any, of clinical testing for HPV by DFH remains to be defined.

Adolescent↗
PubMed1992

Peripheral CA 125 levels in patients with uterine fibroids.

CA 125, a marker of ovarian cancer, is also increased in otherwise normal women suffering from, for example, pelvic inflammatory disease, endometriosis and adenomyosis. The tissues suspected of producing CA 125 in normal women include the endometrium, the ovary and the peritoneum. This study was based on the hypothesis that uterine myomata would distend the peritoneum covering the uterus and thereby increase the peripheral levels of CA 125. To verify this hypothesis we measured CA 125 by an immunoradiometric assay in eight normal women every second day throughout the cycle and in 26 women with uterine fibroids before and after hysterectomy and at 8 and 12 weeks during gonadotrophin releasing hormone (GnRH) analogue therapy. In normal women no difference was observed between CA 125 levels in the follicular phase or in the luteal phase of the cycle. Over one-third (10/26) of the patients with uterine fibroids had increased (greater than 90th centile of the controls) levels of CA 125 before GnRH therapy or hysterectomy. Removal of the uterus or administration of GnRH significantly decreased peripheral concentrations of CA 125 to levels below those observed in normal women. Furthermore, a significant positive correlation was observed between the levels of CA 125 and the volume of myomata as assessed by ultrasound. We conclude that in those cases of uterine fibroids where CA 125 is increased, monitoring this parameter during GnRH therapy is a good indirect measurement of regression of myomata.

Adult↗
PubMed1992

Serum and intracellular magnesium during normal pregnancy and in patients with pre-eclampsia.

OBJECTIVE: To determine the serum and lymphocyte magnesium concentrations during normal pregnancy and to compare the magnesium status in the third trimester of pregnancy between women with normal pregnancy and those with gestational hypertension (GH) or pre-eclampsia (PE). DESIGN: A prospective cross-sectional study followed by a prospective comparative study. SETTING: Department of Obstetrics and Gynecology, Department of Pediatrics and Genetics, Hôpital Cantonal Universitaire Genève, Switzerland. SUBJECTS: Seventy-one healthy pregnant women, with normal pregnancies between 6 and 38 weeks gestation. The second part included 43 women in the third trimester of pregnancy, 11 had GH, 11 had PE and 21 formed the comparison group of healthy normotensive women. MAIN OUTCOME MEASURES: Total serum and intralymphocytic Mg concentrations and urinary Mg excretion. RESULTS: There was a progressive reduction in total serum magnesium concentrations during normal pregnancy, thought to be partly due to haemodilution, because the decline in concentration of serum proteins paralleled that of Mg (P less than 0.001). In the three groups studied in the third trimester the serum Mg concentration was very similar in the GH and the comparison groups, but it was significantly higher in the PE group (P less than 0.01). The intralymphocytic Mg concentrations and the urinary Mg excretion were similar in all three groups. In five patients treated with MgSO4 there was a large increase in the serum Mg concentration and in the urinary Mg excretion. The intralymphocytic Mg concentration remained remarkably stable. CONCLUSIONS: Our data does not support the conclusion that Mg deficiency is the primary cause of pre-eclampsia.

Cross-Sectional Studies↗
PubMed1991

Changes in beta 1- and beta 2-adrenergic receptor mRNA levels in brown adipose tissue and heart of hypothyroid rats.

The aim of the present work was to study the effect of hypothyroidism on the expression of the beta-adrenergic receptor (beta-AR) in interscapular brown adipose tissue and heart. The total density of plasma membrane beta-AR per tissue is decreased by 44% in hypothyroid rat interscapular brown adipose tissue and by 55% in hypothyroid rat heart compared with euthyroid controls. The effects of hypothyroidism on the density of both beta 1- and beta 2-AR subtypes were also determined in competition displacement experiments. The densities of beta 1- and beta 2-AR per tissue are decreased by 50% and 48% respectively in interscapular brown adipose tissue and by 52% and 54% in the heart. Northern blot analysis of poly(A)+ RNA from hypothyroid rat interscapular brown adipose tissue demonstrated that the levels of beta 1- and beta 2-AR mRNA per tissue are decreased by 73% and 58% respectively, whereas in hypothyroid heart, only the beta 1-AR mRNA is decreased, by 43%. The effect of hypothyroidism on the beta 1-AR mRNA is significantly more marked in the interscapular brown adipose tissue than in the heart. These results indicate that beta-AR mRNA levels are differentially regulated in rat interscapular brown adipose tissue and heart, and suggest that the decrease in beta-AR number in interscapular brown adipose tissue and heart of hypothyroid animals may in part be explained by a decreased steady-state level of beta-AR mRNA.

Adipose Tissue, Brown↗
PubMed1991

Effects of a peroxisome proliferator on beta-oxidation and overall energy balance in obese (fa/fa) rats.

The aim of the study was to examine in the obese Zucker (fa/fa) rats the effect of a peroxisome proliferator nafenopin on liver and brown adipose tissue peroxisomal and mitochondrial beta-oxidation enzyme activities and on the overall energy dissipation. A 17-day nafenopin treatment increased liver wet weight 2.1-fold and liver total acyl-CoA oxidase and mitochondria beta-oxidative activities 32- and 4.6-fold, respectively. It increased the interscapular brown adipose tissue (IBAT) acyl-CoA oxidase activity 2.1-fold but had no effect on the mitochondria beta-oxidative activity. Because nafenopin was found to decrease food intake by 22%, obese nafenopin-treated rats were compared with a group of obese pair-fed rats. Both food restriction and nafenopin treatment decreased body weight gain, but a decrease (14%) in fat content was only observed in nafenopin-treated rats. Food restriction of obese rats decreased the mean metabolic rate by 13%, and nafenopin treatment prevented this decrease. Both food restriction and nafenopin treatment decreased the mean daily respiratory quotient (RQ). However, the RQ of nafenopin-treated rats was steadily lower than that of control, whereas that of food-restricted rats was the same as that of control animals during the feeding period and decreased when food supply was exhausted. The increase in liver and IBAT fatty acid beta-oxidative activities may be the cause of the decreased lipid accretion measured in obese rats.

Adipose Tissue↗
PubMed1991

Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue.

The peripheral mechanisms by which ephedrine and caffeine influence thermogenesis were investigated in innervated rat interscapular brown adipose tissue (IBAT) by assessing its rate of oxygen consumption (MO2) in vitro. Dose-response measurements with tissues from intact or sympathectomized (6-OHDA) animals indicate that the thermogenic effects of low concentrations of ephedrine and also of caffeine are entirely dependent upon the presence of intact sympathetic nerve endings, and thus depend on presynaptic mechanisms. Direct postsynaptic stimulation of thermogenesis is only apparent at much higher concentrations, namely greater than 1 microM for ephedrine and greater than 2mM for caffeine. At subminimal concentrations that neither ephedrine nor caffeine influenced basal tissue respiration, they induced a 4-5-fold increase in basal MO2 when administered in combination, a synergistic response prevented by pre-treatment of the rat with 6-OHDA. Synergistic increases in IBAT respiration were also obtained when subminimal concentration of ephedrine was added to 3-propylxanthine (a specific inhibitor of phosphodiesterase), to 8-phenyltheophylline (a potent adenosine receptor antagonist) or to adenosine deaminase (for enzymatic inactivation of endogenous adenosine). Conversely, the marked synergism in thermogenic response with ephedrine + caffeine was reduced in the presence of 2-chloroadenosine (an adenosine analogue). In tissues from fasted rats, the ephedrine + caffeine synergism in thermogenic response, although attenuated, was nevertheless present. These studies therefore demonstrate that ephedrine, at doses comparable with therapeutic use, stimulates thermogenesis in BAT via sympathetically released NA. In addition, a synergistic interaction between caffeine and ephedrine on BAT thermogenesis is explained by ephedrine's enhancement of sympathetic neuronal release of NA, together with caffeine's dual ability to antagonize adenosine and to inhibit cellular phosphodiesterase activity.

2-Chloroadenosine↗
PubMed1990

Role of corticosterone in adaptive changes in energy expenditure during refeeding after low calorie intake.

We examined the importance of corticosterone in elevated efficiency of energy utilization during refeeding after low food consumption. Energy balance studies during refeeding (over periods of 14 or 16 days) were conducted in rats previously food restricted for 16 days at 50% of normal food intake. Comparisons made with nonrestricted weight-matched controls after validation studies indicated that 2-wk-younger weight-matched controls had similar maintenance energy requirements and similar efficiency of energy utilization above maintenance (i.e., net efficiency) to nonrestricted age-matched controls. Results indicate that relative to controls refeeding after low food consumption was associated with enhanced energy conservation underlain by a 16-18% reduction (P less than 0.001) in total energy expenditure over a 14-day period. This metabolic adaptation for energy conservation resulted in a threefold increase (P less than 0.001) in body fat accretion but no difference in body protein deposition. Bilateral adrenalectomy (ADX) 2 days before refeeding reduced differences in energy expenditure between refed group and controls from 18 to 8% (P less than 0.01) and attenuated body fat gain from a three- to twofold increase (P less than 0.001) above control group. Effects of ADX were prevented by daily corticosterone replacement. Data suggest that after a period of low calorie intake an adaptive neurohormonal switching mechanism facilitates replenishment of fat stores during refeeding. This metabolic reorientation (characterized by an adaptive fall in energy expenditure) has both an adrenal as well as a nonadrenal component, because it is partially reversed by prior bilateral ADX, an effect attributed to removal of corticosterone-induced inhibition of thermogenesis.

Adrenalectomy↗
PubMed1990

Underlying mechanisms of atrophic state of brown adipose tissue in obese Zucker rats.

The mechanisms involved in brown adipose tissue (BAT) atrophy in obese rats were investigated. In urethan-anesthetized adult obese (fa/fa) and lean (Fa/?) rats, colonic temperature (Tc), interscapular BAT (IBAT) temperature (TIBAT), and the TIBAT-Tc gradient were measured after microknife cut in the prepontine region and during norepinephrine (NE) infusion. The knife cut tests the neural control of IBAT since it suppresses a tonic inhibition of thermogenesis revealing a sustained reflex stimulation of BAT. The NE infusion tests the metabolic capacity of BAT. In 22 degrees C-acclimated lean rats, the cut induced marked hyperthermia, TIBAT that rose faster than Tc, and a reversed temperature gradient. By contrast, in the obese rat, the cut had practically no effect, and NE infusion caused only slight increases in Tc and TIBAT. In cold-acclimated obese rats, an almost complete response to NE infusion and a partial response to knife cut were observed. After adrenalectomy, the responses were similar in lean and obese rats. An operational model to account for these results and for the deficit in diet-induced thermogenesis in fa/fa rats is proposed.

Adipose Tissue↗
PubMed1989

Peroxisomal oxidative capacity of brown adipose tissue depends on the thyroid status.

The induction of hypothyroidism in rats by methimazole affects interscapular brown adipose tissue (IBAT) mitochondrial and peroxisomal enzyme activities in opposite directions. Hypothyroidism, indeed, decreases both mitochondrial succinate dehydrogenase and beta-oxidation total activities by 35 and 45%, respectively and increases peroxisomal catalase and acyl coenzyme A (acyl CoA) oxidase total activities 3.2- and 1.6-fold, respectively. Administration of a thyroid hormone analogue (3'-isopropyl-3,5-diiodo-L-thyronine) prevents these enzymatic modifications. The effects of hypothyroidism on IBAT mitochondrial enzyme activities seem to be direct, i.e. due to the lack of thyroid hormones, while those on peroxisomal enzyme activities might be indirect, i.e. secondary to the increased thermogenic needs of the rat and mediated by adrenergic stimulation. It is noteworthy that the indirect effects of hypothyroidism on peroxisomes are not observed in liver where acyl CoA oxidase activity is in fact decreased by 40%. In hypothyroid rat IBAT, administration of the peroxisome proliferator nafenopin does not further stimulate the already increased peroxisomal enzyme activities and does not inhibit the already decreased mitochondrial enzyme activities.

Acyl Coenzyme A↗