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Biomedical subjects

L Girardier

Publications and source records attributed to L Girardier.

At least 37 records · Page 2Linked to original sources
PubMed1993

24 hour energy expenditure several months after weight loss in the underfed rat: evidence for a chronic increase in whole-body metabolic efficiency.

The existence and quantitative contribution of an adaptive increase in whole-body metabolic efficiency in response to low caloric intake was examined after prolonged underfeeding in the rat. 24h energy expenditures (EE) and body composition were measured in chronically underfed rats which had been maintaining a stable body weight for several months after an initial period of substantial weight loss. Comparisons were made with ad libitum fed controls. The mean coefficient of variation for daily EE, assessed over three consecutive days, was 3% (range 1.7-4.0%) in the control group and 1.6% (range 0.7-2.1%) in the chronically underfed group, and hence reflect steady state conditions. Body composition was determined by chemical analysis, and as a proportion of body weight (BW), the fat content in the underfed group was reduced by 40% whereas lean body mass was significantly higher by 8%. Independently of the criteria utilized for metabolically active mass, 24h EE was lower in the underfed group than in controls, by 17%, 14% and 8% as a function of BW0.66, BW0.75 and lean body mass respectively (P < 0.01). Underfeeding was also associated with a substantial reduction in the level of external work, but in ad libitum fed animals similar reductions in external work (induced by limiting locomotion) failed to alter 24h EE significantly. Taken together, these studies provide evidence for an increased metabolic efficiency in response to low calorie intake well beyond the period of dynamic weight loss.

Adipose Tissue↗
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

Influence of dietary composition on energy expenditure during recovery of body weight in the rat: implications for catch-up growth and obesity relapse.

The influence of dietary composition on whole-body energetics was examined during the first 2 weeks of isocaloric refeeding after low food intake in a rat model. The high energetic efficiency and energy partitioning toward fat accretion characteristic of this refeeding period were unaltered by (1) dietary fat levels varying between 6% and 30% of energy intake; (2) protein levels between 15% and 40%; (3) carbohydrate types (glucose v fructose v sucrose v starch v unrefined carbohydrate); and (4) diets containing 30% fat but differing in fatty acid composition (long-chain triglycerides [LCT] v medium-chain triglycerides [MCT] v oleic v linoleic v alpha-linolenic metabolites eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] omega-3 fatty acids). Changes were only observed for extreme diets, ie, those deficient in protein or very high in fat. Low-protein diet was the only condition in which the high metabolic efficiency characteristic of the refeeding period was partially suppressed, and this occurred despite a lack of concomitant reduction in body fat deposition. On the contrary, with high-fat diets (> 30% of dietary energy consumption) the elevated efficiency was further increased, an effect that was only partially accounted for by the lower energy cost of body fat gain from high-fat diets. These studies indicate that during body weight recovery, the mechanisms underlying the adaptive increase in metabolic efficiency favoring the replenishment of body fat stores override any effect of food type on thermogenesis, and suggest some convergence in the controlling neural pathway. The implications of these findings vis-a-vis nutritional rehabilitation (catch-up growth) and obesity relapse are discussed.

Animals↗
PubMed1992

Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium.

Mortality rate in mice fed fish oil for 4 weeks was remarkably higher after a very low peroral (PO) challenge with Salmonella typhimurium, as compared with those fed diets rich in either corn oil or hydrogenated coconut oil, or a low fat (chow) diet. None of the surviving mice fed the fish oil diet showed bacterial counts in their spleens, unlike 45.4% to 66.6% of surviving mice fed high fat or low fat diets. The spleens of mice fed fish oil presented the highest number of bacteria 7 days after intraperitoneal infection with the same bacterial strain. Thus, the current studies demonstrate that a diet rich in fish oil decreases host resistance to infection.

Adipose Tissue↗
PubMed1992

Dietary supplementation with fish oil enhances in vivo synthesis of tumor necrosis factor.

Studies reported here investigate the influence of dietary fat types on cytokine production in response to endotoxin (LPS) challenge. Tumor necrosis factor (TNF) serum levels were markedly higher (by 10-fold) in mice fed chronically a diet rich in fish oil rather than either a diet rich in corn or coconut oil or a low fat diet. This in vivo hyper-responsiveness in LPS-induced TNF production following fish oil consumption concorded with similar exaggerated in vitro TNF release from macrophages exposed to LPS. These data suggest that high consumption of fish oils, by virtue of their high content of omega-3 polyunsaturated fatty acids, can lead to an exaggerated production of mediators of inflammation with potentially adverse consequences on the outcome and severity of infectious diseases.

Animals↗
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

Adaptive changes in energy expenditure during refeeding following low-calorie intake: evidence for a specific metabolic component favoring fat storage.

Studies in this report investigate the existence and quantitative contribution of a metabolic component to an apparently elevated efficiency of energy utilization during refeeding following low-calorie consumption. Energy balance during a 25-d refeeding period was assessed in rats that had been food restricted (at 50% of normal intake) for either 30 or 10 d. Relative to weight-matched controls (with comparable lean tissue mass and similar food intake), refeeding following both periods of low food consumption (30 or 10 d) was associated with a 10% reduction in energy expenditure (p less than 0.001). Analysis of body composition revealed that virtually all the energy saved as a result of this metabolic (as opposed to tissue mass) adaptation was deposited as fat rather than protein. After the energy cost for depositing the extra fat is accounted for, the metabolic component represents a net 15% lower energy expenditure when normal food intake is resumed. These adaptive changes in energy expenditure may thus constitute an important mechanism for the rapid replenishment of energy stores in preparation for recurring food shortages and may also underlie the ease with which the obese condition is rapidly reachieved after weight loss.

Adaptation, Biological↗
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↗
PubMed1989

Energy expenditure and diet-induced thermogenesis in presence and absence of hyperphagia induced by insulin.

The influence of experimental hyperinsulinemia on energy intake, energy expenditure, and body composition was investigated in rats treated chronically with high doses of insulin. Energy balance studies, each of 2-wk duration, were conducted with two different long-acting insulins (Protamine and Monotard), administered in the morning (IM), the late afternoon (IA), or both (IMA) and in animals of three different ages, namely in 4-, 8-, and 12-wk-old rats. The results indicate that the level of hyperphagia induced by insulin was markedly influenced by the type of long-acting insulin (P less than 0.001; Protamine greater than Monotard), by age (P less than 0.001; 12 greater than 8 greater than 4 wk), as well as by the timing of insulin administration (P less than 0.002, IMA greater than IM or IA). Body protein deposition was unaltered, but body fat and energy expenditure increased in parallel to the level of hyperphagia. Regression analysis shows a strong linear correlation (r = 0.963) between the change in energy expenditure and the change in energy intake in response to insulin and indicates that approximately 50% of the excess calories consumed was dissipated as heat. In the absence of hyperphagia, however, insulin administration had no effect on energy expenditure nor on energy partitioning. Similarly, the influence of altered meal pattern, induced by administering insulin at different times of the day, was also found to have no impact on energy expenditure. The current investigations therefore refute the notion that high doses of insulin via hyperinsulinemia and/or altered meal pattern have an inhibitory influence on whole body thermogenesis. In contrast, our data demonstrate that the adaptive phenomenon that tends to minimize the accumulation of excess caloric intake, i.e., diet-induced thermogenesis, persists in the hyperinsulinemic state.

Animals↗
PubMed1988

Prepontine knife cut-induced hyperthermia in the rat. Effect of chemical sympathectomy and surgical denervation of brown adipose tissue.

The effect of brown adipose tissue (BAT) denervation on the prepontine knife cut-induced hyperthermia was studied. The knife cut has earlier been shown to induce a steady state hyperthermia of 3 to 4 degrees C, as a result of marked activation of the BAT. Before the lesion, the interscapular BAT (IBAT) temperature was lower than the colonic temperature, but the temperature gradient reversed a few minutes after the lesion and the fractional blood flow increased 12-fold. Bilateral sectioning of the 5 nerves supplying IBAT did not modify either the magnitude or the kinetics of the IBAT hyperthermic response. The IBAT fractional blood flow, which was 15 times higher in denervated than in intact tissue before the lesion, scarcely increased following the lesion despite the sharp increase in the tissue's metabolic activity. Chemical sympathectomy with 6-hydroxydopamine suppressed the hyperthermic response. Propranolol or hexamethonium injected i.v. during the steady state hyperthermia resulted in a rapid drop in IBAT temperature and in a reversal of the gradient between IBAT and colonic temperature both in denervated and in intact IBAT. Injection of desipramine, an inhibitor of noradrenaline reuptake, resulted in itself in an increase of temperature in both intact and denervated tissue, which is circumstantial evidence for the presence of a functional residual innervation in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1988

Evidence for a modulating effect of Na+/H+ exchange on the metabolic response of rat brown adipose tissue.

Membrane potential and intracellular pH (pHi) were simultaneously monitored in rat perifused brown adipose tissue fragments by means of double-barrelled microelectrodes. In parallel experiments, the respiratory rate was measured. The cytosolic pH of unstimulated brown adipocytes was about 0.5 units higher than the value expected for a passive transmembrane distribution of H ions. Isoproterenol (5.10(-10)M) had no effect on pHi and membrane potential while it induced a 3.1 +/- 0.5-fold increase of the respiratory rate. Clonidine (10(-7)M) alone was followed by a cytosolic alkalinization of 0.14 +/- 0.05 pH units with no concomitant increase in the respiratory rate. A mirror image of the intracellular alkalinization induced by clonidine, i.e. an acidification of 0.09 +/- 0.03, was noted by monitoring the extracellular pH. Addition of clonidine in the presence of isoproterenol induced an alkalinization of 0.17 +/- 0.03 pH units and a 7.7 +/- 1.0-fold increase of the respiratory rate. Thus the alkalinizing effect of clonidine developed despite a massive increase in CO2 production. Pretreatment of the preparation with amiloride (10(-3)M), an inhibitor of Na+/H+ exchange, completely prevented the alkalinization and markedly reduced the potentiating effect of clonidine on the isoproterenol-induced respiratory rate. The results obtained are compatible with the hypothesis of a modulating effect of Na+/H+ exchange on the brown adipocyte metabolic response to catecholamine stimulation.

Adipose Tissue, Brown↗
PubMed1988

Increased plasma clearance rate of thyroxine despite decreased 5'-monodeiodination: study with a peroxisome proliferator in the rat.

In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl-diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation. In addition, nafenopin was found to be a weak competitor of T4 binding to serum proteins, leading to a small increase in the free T4 fraction which might also contribute to the increased T4 PCR. The decrease in T3 PCR remains to be explained.

Adipose Tissue, Brown↗
PubMed1987

Hyperthermia induced by pre-pontine knife-cut: evidence for a tonic inhibition of non-shivering thermogenesis in anaesthetized rat.

Temperature of colon, interscapular brown adipose tissue (IBAT) and paw skin (index of vasomotor activity) were monitored before and after microwire knife lesions at the pre-pontine or/and the post-mammillary levels in the urethane-anaesthetized rats at room temperature of 23-24 degrees C. Following the pre-pontine, but not the post-mammillary cut, colonic and IBAT temperatures increased by 3-4 degrees C within 90-240 min. IBAT temperature rose faster with a shorter latency and attained a higher steady-state value than colonic temperature; skin temperature, however rose by only 0.8 degrees C. A procaine microinjection into the pre-pontine area transiently increased by more than 1 degree C both colonic and IBAT temperatures, with similar kinetics as for the knife cut. Cardiac output distribution was measured using radiolabelled microspheres. Brown adipose tissue (BAT) was found to be the only organ to which the fractional blood flow increased dramatically (12 times over baseline value) during the development of hyperthermia. Propanolol, injected after the hyperthermia had fully developed, decreased IBAT and then colonic temperatures. Hexamethonium decreased both colonic and IBAT temperatures with a concomitant rise in skin temperature while tubocurarine was without effect. It is concluded that the hyperthermia observed after the pre-pontine lesion results from an increased sympathetic stimulation of BAT thermogenesis triggered by the release of a tonic inhibitory control on its heat production. Such an inhibitory system would be located somewhere between the lower midbrain and the upper pons.

Adipose Tissue, Brown↗