Biomedical subjects

A Géloën

Publications and source records attributed to A Géloën.

At least 19 recordsLinked to original sources

PubMed2005

Covalent binding of 15-deoxy-delta12,14-prostaglandin J2 to PPARgamma.

Since 15-deoxy-delta(12,14)-prostaglandin J(2) (15dPGJ(2)) has been identified as an endogenous ligand of PPARgamma thus inducing adipogenesis, it has been reported to play active parts in numerous cellular regulatory mechanisms. As 15dPGJ(2) has been shown to covalently bind several peptides and proteins, we investigated whether it also covalently binds PPARgamma. We first observed that after incubation of 15dPGJ(2) with recombinant PPARgamma, the quantity of free 15dPGJ(2) measured was always lower than the initial amount. We then measured the ability of the labeled agonist rosiglitazone to displace the complex PPARgamma(2)/15dPGJ(2) obtained after pre-incubation. We observed that the binding of rosiglitazone was dependent on the initial concentration of 15dPGJ(2). Finally using MALDI-TOF mass spectrometry analysis, after trypsinolysis of an incubate of the PPARgamma(2) ligand binding domain (GST-LBD) with 15dPGJ2, we found a fragment (m/z = 1314.699) corresponding to the addition of 15dPGJ(2) (m/z = 316.203) to the GST-LBD peptide (m/z = 998.481). All these observations demonstrate the existence of a covalent binding of 15dPGJ(2) to PPARgamma, which opens up new perspectives to study the molecular basis for selective activities of PPARs.

Adipocytes↗

PubMed2005

Effects of oxidative stress on adiponectin secretion and lactate production in 3T3-L1 adipocytes.

Obesity is an increasing nutritional disorder in developed countries, and oxidative stress has been identified as a key factor in numerous pathologies such as diabetes, inflammation, and atherosclerosis, which are favored by obesity. The objective of the present study was to investigate the effects of oxidative stress in 3T3-L1 adipose cells on two parameters involved in metabolic complications associated with obesity, namely adiponectin secretion and lactate production. Differentiated 3T3-L1 adipose cells were exposed to increasing concentrations of glucose oxidase. 4-Hydroxynonenal (4-HNE), a relevant lipid peroxidation by-product which may affect several metabolic processes in making covalent adducts with various molecules; adiponectin secretion; and lactate production were measured in response to glucose oxidase exposure. Results show an inhibition of adiponectin mRNA expression by glucose oxidase and a significant inverse correlation between 4-HNE formation and adiponectin secretion. Furthermore, 4-HNE alone inhibits adiponectin production by 3T3-L1. On the other hand, glucose oxidase and 4-HNE significantly stimulated lactate production by 3T3-L1 adipocytes. These results demonstrate that adipose cells are highly sensitive to oxidative stress, with subsequent decreased adiponectin secretion and increased lactate production, two events involved in the development of insulin resistance.

3T3-L1 Cells↗

PubMed2003

Resistance to obesity in Lou/C rats prevents ageing-associated metabolic alterations.

AIMS/HYPOTHESIS: Ageing is associated with metabolic alterations characterised by changes in energy expenditure, obesity, leptin and insulin resistance. The Lou/C rat, an inbred strain of Wistar origin, is presented as both an obesity-resistant rat and a model of healthy ageing. METHODS: To characterise the mechanisms underlying obesity resistance in Lou/C rat, we measured food intake and energy expenditure by indirect calorimetry at 1, 6, 12, 18, and 24 months of age. Moreover, plasma insulin and leptin concentrations were assessed by radioimmunoassay in Lou/C and Wistar rats throughout their life span. RESULTS: Compared to Wistar rats, Lou/C rats presented a higher food intake only at 24 months of age and they had a higher energy expenditure at 6 and 12 months of age (+21% and +14%, respectively). Plasma insulin concentration increased markedly in 18- and 24-month-old Wistar rats, but remained stable during ageing in Lou/C rats. From the age of 6 months, the plasma leptin concentrations in Wistar rats were higher than in Lou/C rats of the same age (four-, seven-, five- and threefold higher at 6, 12, 18, 24 months of age, respectively). CONCLUSION/INTERPRETATION: Compared to Wistar rats, Lou/C rats did not develop insulin resistance as confirmed by a higher glucose infusion rate during the hyperinsulinaemic-euglycaemic clamp. These data provide evidence that insulin resistance is associated with the excess of adipose tissue in Wistar rats. Not only Lou/C rats present a higher median life span than Wistar rats (+20%), but they also show a healthy ageing process considering fat accretion and insulin resistance.

Aging↗

PubMed2003

Activation of brown adipose tissue thermogenesis increases slow wave sleep in rat.

Considering the thermoregulatory role of slow wave sleep (SWS), we wondered whether the sole increase of brown adipose tissue (BAT) thermogenesis could enhance this sleep state. We tested this hypothesis by administering to rats an agonist (BRL 37,344) of the beta-3 adrenoceptor subtype that is massively localized in BAT cell membrane and that is known to activate BAT thermogenesis. Sleep was electrographically characterized. The temperature of interscapular BAT (Tibat) and cortex (Tco) were also assessed. Tibat significantly increased 2-3 h after BRL injection (but not Tco), concomitantly with SWS (+56-57%). At the maximum of Tibat, a significant positive correlation was found between their changes and those of SWS. We demonstrated for the first time that sleep (and especially SWS) can be affected by the specific activation of BAT.

Adipose Tissue, Brown↗

PubMed2002

Increased intraabdominal adipose tissue mass in fructose fed rats: correction by metformin.

Summary. The aim of the present study was to investigate the effect of metformin on insulin sensitivity, adipose tissue mass and sympathetic nervous system (SNS) activity in fructose fed rats. Male Sprague-Dawley rats were fed for six weeks either on a standard diet (C group) or on a high-fructose diet (F group, 10% in drinking water). In each group, half of the animals received metformin in drinking water for the last 4 weeks (500 mg/kg x day, C+M and F+M). Hyperinsulinemic-euglycemic clamps (6 mU insulin/kg.min) were performed on awake unrestrained rats to test insulin resistance. Six-week fructose diet induced a reproducible insulin resistance (31.1 +/- 1.9 C vs 22.5 +/- 3.2 mg glucose/kg.min F, p<0.05). Metformin treatment prevented insulin resistance (31.1 +/- 1.9 C vs 30,2 +/- 1.8 mg glucose/kg x min F+M, ns). To measure SNS activity, rats received, ten minutes before sacrifice, an i.p. injection of NSD (m-hydroxybenzylhydrazine, inhibitor of DOPA decarboxylase, 100 mg/kg). DOPA accumulation was used as an index of SNS activity and measured in superior cervical, coeliac ganglias, retroperitoneal and epidydimal adipose tissues. SNS activity was increased in F group only in coeliac ganglia (16.8 +/- 1.1 C vs 22.6 +/- 2.2 ng DOPA/ganglia, F group, p<0.05) and not in superior cervical ganglia (8.4 +/- 0.7 C vs 8.6 +/- 0.7 ng DOPA/ganglia, F group, ns). Metformin had no effect on SNS activity in coeliac ganglia of control animals (15.9 +/- 1.7 C+M vs 16.8 +/- 1.1 ng DOPA/coeliac ganglia C, ns) but prevented the increase in SNS activity in fructose fed animals (22.6 +/- 2.2 F vs 16.3 +/- 2.8 ng DOPA/coeliac ganglia F + M). In fructose fed rats, metformin significantly increased sympathetic activity in retroperitoneal white adipose tissue (RPWAT) resulting in a marked decrease in depot mass but had no effect on epidydimal WAT. In conclusion, our results demonstrate that fructose diet caused a selective increase of SNS activity in coeliac ganglia. Metformin increased SNS activity in RPWAT resulting in a significant reduction in RPWAT mass, lowered SNS activity in coeliac ganglia to control values and restore whole body insulin sensitivity.

Adipose Tissue↗

PubMed2001

Propofol-induced cytochrome P450 inhibition: an in vitro and in vivo study in rats.

Propofol, a widely used anesthetic drug, is known to inhibit cytochrome P450 activities in vitro. The goal of this study was to compare cytochrome P450 activities in vitro and in vivo in presence of propofol. In vitro (liver microsomes and freshly isolated hepatocytes), cytochrome P450 IA2 and IIB1 activities were measured as the production of resorufin from ethoxy- and pentoxyresorufin, respectively, in presence of various concentrations of propofol. In vivo, cytochrome P450 activities were assessed as the production of 13CO2 from 13C-aminopyrine injected intravenously, during acute administration or after chronic treatment. In vitro results confirmed the dose-dependent inhibitory effect of propofol on cytochrome P450 activities, both on liver microsomes and isolated hepatocytes. In vivo, the acute administration of propofol induced a significant decrease of 13C-aminopyrine metabolism. Chronic treatment with propofol induced a significant inhibition of 13C-aminopyrine metabolism only after 2 weeks. No enzyme induction was observed. In conclusion, our results demonstrate that propofol inhibits cytochrome P450 also in vivo. Drug interactions may thus occur during propofol administration.

Aminopyrine↗

PubMed2001

Simulated weightlessness alters the nycthemeral distribution of energy expenditure in rats.

The energy metabolism adaptations to simulated weightlessness in rats by hindlimb tail suspension are unknown. 12 male rats were assigned to 7 days of isolation, 7 days of habituation to the suspension device, 10 days of simulated weightlessness, and 3 days of recovery. The 24-hour energy expenditure was measured by continuous indirect calorimetry. We calculated the 12-hour energy expenditure during the active (night) and inactive (day) periods, the minimal observed metabolic rates with the day values taken as an index of the basal metabolic rate, and the non-basal energy expenditure representing the cost of physical activity plus the diet-induced thermogenesis. Suspension did not change the mean 24-hour energy expenditure (360.8+/-15.3 J min(-1) kg(-0.67)), but reduced the night/day difference by 64 % (P<0.05) through a concomitant drop in night-energy expenditure and increase in day values. The difference between night and day minimal metabolic rates was reduced by 81 % (P<0.05), and the transient rise in day values suggests an early and moderate basal metabolic rate increase (9 %). An overall 19 % reduction in non-basal energy expenditure was observed during simulated weightlessness (P<0.05), which was mainly attributable to a reduction in the cost of physical activity. 3 days of recovery restored the night/day differences but increased the 24-hour energy expenditure by 10 % (P<0.05). In conclusion, hindlimb tail suspension in rats did not alter the 24-hour energy expenditure, but it transiently increased the basal metabolic rate, and altered both the energy expended on physical activity and the nycthemeral distribution of motor activity. These data suggest that the circadian rhythms of energy expenditure are affected during simulated weightlessness.

Animals↗

PubMed2000

Validation of the doubly labeled water method in rats during isolation and simulated weightlessness.

Total energy expenditure (TEE) of rats during simulated microgravity is unknown. The doubly labeled water method (DLW) reliably measures TEE, but the results depend on the methods of calculation. These methods were validated and appraised by indirect calorimetry in eight rats during isolation (7 days) and simulated microgravity (10 days). There were no effects on CO(2) production in the method used to derive constant flux rates as in the regression models. r(CO(2)) estimates were dependent on the assumed fractionation processes, the derivation of constant flux rate methods, and the selected pool models. Use of respiratory or food quotients did not influence TEE estimations, which were similar during isolation and simulation. During either isolation with growth or simulation with a stabilized mass, the one-pool model of Speakman (Speakman JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) resulted in the more reliable validation (0.8 +/- 2.2 and 2.2 +/- 3.4% vs. calorimetry, respectively). However, during simulation, agreement was also observed with the single pool model of Lifson (Lifson N, Gordon GB, and McClintock R. J Appl Physiol 7: 704-710, 1955) (-2.5 +/- 2.5%), and two two-pool models [Schoeller (Schoeller DA. J Nutr 118: 1278-1289, 1988) (0.5 +/- 3.1%) and Speakman (Speakman, JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) (-1.9 +/- 2.7%)]. This latter finding seems linked to the stable body mass and to fractionation consideration close to the single-pool model of Speakman. During isolation or simulated microgravity, the other equations underestimated TEE by 10-20%.

Animals↗

PubMed1999

Differential regulation of uncoupling protein-1, -2 and -3 gene expression by sympathetic innervation in brown adipose tissue of thermoneutral or cold-exposed rats.

The control of uncoupling protein-1, -2 and -3 (UCP-1, UCP-2, UCP-3) mRNA levels by sympathetic innervation in rats was investigated by specific and sensitive RT-PCR assays. In rats reared at thermoneutrality (25 degrees C), unilateral surgical sympathetic denervation of interscapular brown adipose tissue (BAT) markedly reduced the UCP-1 mRNA level (-38%) as compared with the contralateral innervated BAT pad, but was without significant effect on UCP-2 and -3 mRNA levels. Cold exposure (7 days, 4 degrees C) markedly increased UCP-1 (+180%), UCP-2 (+115%) and UCP-3 (+195%) mRNA levels in interscapular BAT. Unilateral sympathetic denervation prevented the cold-induced rise in BAT UCP-1 and UCP-2 mRNAs, but not that in BAT UCP-3 mRNA. Results were confirmed by Northern blot analysis. These data indicate a differential endocrine control of UCP-1, UCP-2 and UCP-3 gene expression in rat BAT both at thermoneutrality and during prolonged cold exposure.

Adipose Tissue, Brown↗

PubMed1999

Effects of ethanol and diabetes on galactose oxidative metabolism and elimination in rats.

Blood galactose clearance after an intravenous galactose load has been widely used for years as an index of liver function. We developed a noninvasive [13C]galactose breath test, which explores galactose oxidative metabolism; this test is well correlated with liver fibrosis in patients with chronic viral hepatitis. The goal of this study was to evaluate the influence of nonhepatic factors such as diabetes and ethanol on whole-body galactose clearance (measured as the serum galactose elimination capacity test) and oxidative metabolism (measured as the [13C]galactose-induced breath 13CO2 production) in rats. Acute ethanol administration induced a significant decrease of galactose clearance and 13CO2 production. There was a significant correlation between the amount of ethanol given and the inhibition of galactose metabolism (R2 = 0.72, p < 0.0001). In streptozotocin-induced diabetic rats, the [13C]galactose-induced breath 13CO2 production was significantly reduced (p < 0.0001) and normalized by insulin treatment. However, diabetes did not decrease whole-body galactose clearance, indicating an isotopic dilution of [13C]glucose produced from [13C]galactose metabolism into the enlarged glucose pool. These results must be taken into account when using the [13C]galactose breath test as a quantitative liver function test.

Animals↗

PubMed1998

Effects of chronic treatment with noradrenaline or a specific beta3-adrenergic agonist, CL 316 243, on energy expenditure and epididymal adipocyte lipolytic activity in rat.

1. The effects of 7 days exposure to a specific beta3-adrenergic agonist, CL 316 243 (1 mg/kg x 24 hr), or to the physiological hormone, noradrenaline (5 mg/kg x 24 hr), were tested on energy expenditure and on in vitro lipolysis in male Sprague-Dawley rats. 2. At the second day of treatment, the total energy expenditure and the resting metabolic rate were increased by 20 and 30%, respectively, in the CL-treated group. Under the same conditions, a dose five times higher of NA increased the resting metabolic rate by 11% without any significant change in the total daily energy expenditure. 3. The CL-treated group showed a lower weight gain, correlated with a significant reduction in retroperitoneal adipose tissue weight. Both treatments resulted in a marked desensitization (increased EC50 values) of the NA stimulated lipolysis of epididymal adipocytes. The effects of both treatments on maximal lipolysis were opposite. Indeed, chronic NA-treatment decreased the responsiveness of lipolysis while chronic treatment with CL increased the maximal stimulation of lipolysis to NA. Furthermore, dose-response curve for CL on lipolysis showed a marked functional desensitization of beta3-adrenergic response. 4. Our results demonstrate the high selectivity of beta3-adrenergic agonists to stimulate whole body energy expenditure and lipid mobilization in rodents. The present results point out for the first time an adrenergic desensitization of the lipolytic response after chronic administration of a beta3-agonist.

Adipocytes↗

PubMed1998

Alpha-1 adrenergic stimulation of glucose uptake in rat white adipocytes.

We recently demonstrated that adipocyte lactate production depends on alpha-1 adrenergic control and that adipocytes can produce lactate even when insulin-stimulated glucose uptake is markedly impaired. This prompted us to investigate the glucose uptake in response to an alpha-1 adrenergic stimulation. We measured the adrenergic regulation of glucose uptake by adipocytes isolated from epididymal white adipose tissue using agonists (norepinephrine, phenylephrine and isoproterenol) and antagonists (prazosin and propranolol) of alpha-1 and beta adrenoceptor subtypes. Our results show that the maximal glucose uptake obtained in the presence of 10(-8) M norepinephrine is partially inhibited by prazosin (10(-6) M, 57%) or propranolol (10(-6) M, 52%) suggesting that glucose uptake is subjected to both alpha-1 and beta regulation. Indeed, our findings show that glucose uptake is dose-dependently increased by phenylephrine. This stimulation is totally inhibited by prazosin (10(-6) M). Isoproterenol stimulated glucose uptake. The stimulation of glucose uptake by isoproterenol is totally inhibited in the presence of propranolol (10(-6) M) in the incubation medium. Our results demonstrate for the first time that alpha-1 adrenergic subtype is involved in the regulation of glucose uptake by white adipocytes.

Adipocytes↗

PubMed1997

Effect of aging on norepinephrine and phenylephrine stimulated lactate production by white adipocytes.

We have recently demonstrated that adipose tissue can produce lactate independently of lipolysis in insulin-resistant rats and that lactate production depends on alpha 1-adrenergic stimulation. In this study, we have investigated the influence of aging on norepinephrine-and-phenylephrine-stimulated lactate production and glycerol production. We showed that basal and norepinephrine stimulated lactate production were significantly increased in adipocytes isolated from old vs. young rats (0.165 +/- 0.006 vs. 0.055 +/- 0.008 for basal and 0.567 +/- 0.026 vs. 0.277 +/- 0.019 mumol lactate/10(6) cells/15 minutes for norepinephrine-stimulated lactate production, respectively, p < 0.05). The sensitivity of lactate production to norepinephrine stimulation in adipocytes isolated from old rats was significantly decreased (EC50 = 523 +/- 63.7 vs. 46.7 +/- 6.34 nM, respectively, p < 0.05). Maximal lactate production obtained with norepinephrine and phenylephrine was not significantly different in either group (0.567 +/- 0.026 vs. 0.520 +/- 0.036 in old and 0.277 +/9 0.019 vs. 0 275 +/- 0.017 mumol/10(6) cell/15 minutes in young rats, respectively, ns). Lactate production by adipocytes isolated from old rats were significantly less sensitive to phenylephrine stimulation compared with young (EC50 = 3.67 +/- 1.16 vs. 0.07 +/- 0.01 nM, respectively, p < 0.05) indicating that the effects of aging on norepinephrine and phenylephrine stimulation were probably induced by a decreased number of alpha 1-adrenoceptors. The mechanism by which aging increases adipocyte responsiveness of lactate production has not yet been elucidated.

Adipocytes↗

PubMed1997

Short-term cold-exposure does not improve insulin sensitivity in rats.

Effects of noradrenergic activation induced by short-term cold-exposure (7 days at 4 degrees C) on whole-body glucose utilization and tissue glucose uptake were investigated in rats. Measurements were realized on anesthetized normothermic animals at four different levels of insulinemia, within physiological range, allowing calculation of insulin sensitivity and responsiveness. Whole-body glucose utilization increased as a logarithmic function of insulinemias, and was always higher in cold-exposed than in control rats. However, neither insulin sensitivity nor responsiveness, literally, appeared different between the two groups. In the diaphragm, the only studied working muscle, glucose uptake was largely higher than in restin muscles. At basal insulin concentration, glucose uptake was higher in cold-exposed than in control rats and increased in the two groups with insulinemia. Among resting muscles, glucose uptake was increased by previous cold exposure in gastrocnemius, soleus, and tibialis. However, insulin sensitivity and responsiveness were found augmented only in the two former. In interscapular brown adipose tissue, glucose uptake was largely higher in cold-exposed than in control rats, but no difference could be evidenced in insulin sensitivity or responsiveness. In white adipose tissues, glucose uptake increased with insulinemia. Insulin responsiveness and sensitivity were higher only in the retroperitoneal depot.

Adipose Tissue↗

PubMed1997

Transient upregulation of IGF-I gene expression in brown adipose tissue of cold-exposed rats.

The possible involvement of locally produced insulin-like growth factor I (IGF-I) in the cold-induced hyperplasia of interscapular brown adipose tissue (BAT) was investigated in 2-, 4-, and 7-day cold-exposed (CE, 4 degrees C) rats by measuring BAT IGF-I expression at a time when extensive BAT cell proliferation occurs. By comparison with thermoneutral (25 degrees C) controls, plasma IGF-I decreased in CE rats despite an increased food intake, whereas BAT IGF-I peptide increased markedly to peak after 4 days at 4 degrees C. The ratio of class 1 to class 2 IGF-I mRNA was much higher in BAT than in liver. BAT IGF-I mRNA levels per unit weight total RNA doubled after 2 days at 4 degrees C but decreased thereafter to the level in controls. Upregulation of BAT IGF-I mRNA also occurred in CE rats with a food intake restricted to the level of controls. The transient cold-induced upregulation of BAT IGF-I (per unit weight total RNA) suggests that IGF-I plays a role in the early cold-induced BAT hyperplasia that occurs in vivo.

Adipose Tissue, Brown↗

PubMed1997

[Tissue microdialysis: practical and theoretical aspects].

Microdialysis is now widely used for the study of peripheral tissues. This technique allows the monitoring of metabolites and small molecules from the extracellular compartment as well as local delivery of metabolically active agents to this compartment. The purpose of this review was to present a practical approach (different types of probes, molecular cut-off, perfusion rate, dialysis buffer) and discuss the theoretical aspects of in vivo microdialysis (probe efficiency, recovery, perfusion rate, quantification of tissular metabolism). Our goal was to provide researchers with the practical tools needed for rapid mastery of in vivo tissular microdialysis.

Animals↗

PubMed1997

In situ lipolysis measured by in vivo microdialysis during acute cold exposure.

The lipolytic responsiveness of interscapular white adipose tissue was measured, in male Sprague-Dawley rats (355 +/- 12 g, n = 7), by microdialysis before, during, and after an acute cold exposure (1 h at 4 degrees C). Microdialysis probes were perfused with standard Krebs-Ringer buffer to determine basal and stimulated rates of lipolysis. The concentration of glycerol in the dialysate was measured and considered as the lipolytic index. During the experiment, energy expenditure was measured by indirect calorimetry. Cold exposure at 4 degrees C doubled energy expenditure. At the same time, it resulted in a 2.7-fold increase in glycerol release. The present study shows that microdialysis is a perfectly adapted tool to investigate in vivo regulation of adipose tissue on awake, unrestrained rats.

Adipose Tissue↗

PubMed1996

Continuous monitoring of 13C-aminopyrine metabolism in rats: effects of cold exposure and noradrenaline.

A system was developed to allow constant monitoring of hepatic cytochrome P450 activity in awake and unrestrained rats. A continuous 13C-aminopyrine perfusion was performed, and breath samples obtained for endogenous CO2 production and 13C measurements, to calculate 13C O2 production due to aminopyrine demthylation. Increasing doses of 13C-aminopyrine produced a hyperbolic increase of expired 13CO2, compatible with an in vivo measurement of enzymatic activity. Acute-cold exposure of the rats during 13C-aminopyrine perfusion produced a two-fold increase of endogenous CO2 production, together with a 27% increased 13C-aminopyrine metabolism (p<0.05 vs basal conditions). In contrast, noradrenaline (20 microg/kg BW/min), despite a similar effect on energy expenditure, did not significantly change 13C-aminopyrine metabolism. Acute-cold exposure is known to stimulate both adrenal catecholamine secretion and the sympathetic nervous system. The observed difference in 13C-aminopyrine demthylation during cold exposure and nonadrenaline perfusion, therefore, could be due to a more specific effect of adrenal catecholamines on liver aminopyrine metabolism. These results suggest the possibility of prolonged in vivo monitoring of liver metabolism pathways such as aminopyrine demethylation, thus allowing the study of drug acute interactions with cytochrome P450 system.

Aminopyrine↗