Biomedical subjects

Denis Richard

Publications and source records attributed to Denis Richard.

47 records · Page 3Linked to original sources

PubMed2003

Effects of treadmill running on brain activation and the corticotropin-releasing hormone system.

The present study was conducted to investigate the effects of treadmill running on the corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and CRH-binding protein (CRH-BP) in the brain of rats that were killed either at rest, immediately after 60 min of treadmill running, or 180 min following a 60-min session of intensive exercise. The expression of the neuronal activity marker c-FOS was also determined in the three conditions of this study. The levels of c-FOS mRNA immediately following running were high in the cortex, caudate-putamen, lateral septum, bed nucleus of the stria terminalis, dorsal and medial thalamus, hypothalamus, pontine nuclei, locus coeruleus and hypoglossal nucleus. In most brain regions investigated, excluding the locus coeruleus and the cingulate cortex, c-FOS mRNA expression returned to control levels after 2 h of recovery. The highest concentration of cells co-expressing the protein Fos and CRH mRNA neurons was found in the parvocellular part of the paraventricular nucleus, which also expressed CRH heteronuclear RNA and CRH-R1 mRNA. The medial preoptic area (MPOA), the medial mammillary nucleus and the posterior hypothalamic as well as the somatosensory cortex, the medial geniculate nucleus, the reticulotegmental nucleus, and Barrington's nucleus also co-expressed Fos and CRH mRNA. The expression of CRH-BP gene was induced in the MPOA following running. In summary, the present study demonstrates that treadmill running leads to a strong expression of c-FOS mRNA that is widely distributed throughout the brain. c-FOS mRNA was found in structures of the somatosensory and somatomotor systems, indicating that these regions were activated during exercise. The pattern of distribution of c-FOS mRNA showed similarities with that triggered by neurogenic and systemic stresses. The present results also indicate that treadmill running can strongly activate the hypophysiotropic CRH system, which suggests, in agreement with the pattern of c-FOS mRNA distribution, that treadmill running has a strong stress component.

Animals↗

PubMed2003

PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion.

This study sought to determine whether the adipose depot-specific (subcutaneous [SF] vs. visceral [VF]) action of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists on fat deposition extends to the expression of lipoprotein lipase (LPL) and other key adipose lipid metabolism genes, and whether changes in LPL impact triglyceridemia. Rats were fed a standard diet or an obesity-promoting diet for 3 weeks, with or without treatment with COOH, a nonthiazolidinedione PPAR-gamma agonist. Treatment effects were essentially similar in both dietary cohorts. COOH did not affect weight gain, but increased SF (inguinal) fat mass twofold and reduced VF (retroperitoneal) accretion by half. Corresponding depot-specific alterations were observed in mRNA levels of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD-1) and the thermogenic modulator uncoupling protein 1 (UCP-1). COOH increased brown adipose tissue (BAT) weight and LPL availability by five- to eightfold. In rats refed standard diet after a 24-h fast, COOH reduced the insulin excursion by half. The agonist increased SF LPL activity and mRNA levels, but had no effect on VF LPL. The two- to threefold postprandial increase in plasma triglycerides (TGs) was abrogated in COOH-treated rats, likely in part because of increased LPL in SF and BAT. Thus PPAR-gamma agonist treatment had a powerful, site-specific effect on adipose metabolism and lipid deposition, and greatly impacted the postprandial handling of TG-rich lipoproteins. These depot-specific effects may be mediated by differential regulation of key metabolic genes, including LPL, 11beta-HSD-1, and UCP-1.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2002

Comparative effects of the antipsychotics sulpiride or risperidone in rats. I: bodyweight, food intake, body composition, hormones and glucose tolerance.

Obesity and related metabolic disorders are important side effects of some antipsychotic drugs (APs). The currently available animal model of AP-induced bodyweight gain (BWG) in rats is based on administration of sulpiride (SUL). However, this model has important limitations. For example, SUL is a pure dopamine antagonist, whereas most APs in current clinical use interact with multiple neurotransmitter receptors involved in food intake (FI) and metabolism regulation. Therefore, we evaluated the effects of risperidone (RIS, 0.125, 0.25 or 0.5 mg/kg during 16 days) on BWG and FI in male and female rats. Comparison between RIS (0.5 mg/kg), SUL (20 mg/kg) and vehicle (VEH) during 12 days was also conducted in females. In male rats, RIS did not significantly affect BWG, FI, glucose tolerance or leptin levels, even though prolactin and corticosterone were significantly elevated. In females, both APs significantly increased BWG and FI, but the effect was stronger with SUL. The BWG was significantly associated with an increase in body fat. Serum leptin levels were increased only in SUL-treated rats. The area under the curve for glucose (AUGC) was significantly lower in the SUL group, but it was similar for insulin in all treatment groups. The area under the curve for insulin (AUIC) and BWG positively correlated only in the RIS group. Prolactin and corticosterone were significantly increased by both APs. Serum estradiol levels were significantly increased by RIS but not by SUL, but progesterone levels were similar in both groups. The observed positive correlation between BWG and the AUIC during RIS administration suggests that this agent may represent a better model of AP administration in humans. The animal model of RIS-induced obesity in rats might be improved by testing other doses, route of administration and type of diet.

Animals↗

PubMed2002

How aphids lose their marbles.

Insects provide examples of many cunning stratagems to cope with the challenges of living in a world dominated by surface forces. Despite being the current masters of the land environment, they are at constant risk of being entrapped in liquids, which they prevent by having waxy and hairy surfaces. The problem is particularly acute in an enclosed space, such as a plant gall. Using secreted wax to efficiently parcel and transport their own excrement, aphids were able to solve this problem 200 Myr ago. Here, we report on the physical and physiological significance of this ingenious solution. The secreted powdery wax has three distinct roles: (i) it is hydrophobic, (ii) it creates a microscopically rough inner gall surface made of weakly compacted wax needles making the gall ultra-hydrophobic, and (iii) it coats the honeydew droplets converting them into liquid marbles, that can be rapidly and efficiently moved.

Animals↗

PubMed2002

Contact time of a bouncing drop.

When a liquid drop lands on a solid surface without wetting it, it bounces with remarkable elasticity. Here we measure how long the drop remains in contact with the solid during the shock, a problem that was considered by Hertz for a bouncing ball. Our findings could help to quantify the efficiency of water-repellent surfaces (super-hydrophobic solids) and to improve water-cooling of hot solids, which is limited by the rebounding of drops as well as by temperature effects.

Journal Article↗

PubMed2002

The corticotropin-releasing factor family of peptides and CRF receptors: their roles in the regulation of energy balance.

The corticotropin-releasing factor (CRF) system could play a significant role in the regulation of energy balance. This system, which includes CRF, CRF-related peptides and CRF receptors, is part of a huge network of cells connected to central and peripheral pathways modulating energy metabolism. CRF and CRF-related peptides, which elicit their effects through G-protein-coupled receptors known in mammals as CRF(1) receptor and CRF(2) receptor, are capable of strong anorectic and thermogenic effects. Also supporting a role for the CRF system in the regulation of energy balance are findings demonstrating alterations in this system in obese and food-deprived animals that concur to facilitate energy deposition. In recent years, great progress has been made in understanding the specific physiological roles of the CRF system. In that respect, the discovery of urocortins II and III, two endogenous ligands of the CRF(2) receptor, and the development of selective and long-acting antagonists for the CRF receptors, have led to a better comprehension of the role of the CRF system in the regulation of energy balance. Although there are still important unresolved issues in the field of CRF research, the progress made recently warrants investigations aimed at evaluating the CRF system as a potential target for anti-obesity drugs.

Animals↗

PubMed2002

Neuronal activation and corticotropin-releasing hormone expression in the brain of obese (fa/fa) and lean (fa/?) Zucker rats in response to refeeding.

The present study was conducted to investigate the pattern of neuronal activation and corticotropin-releasing hormone (CRH) expression in fed, food deprived and refed lean (Fa/?) and obese (fa/fa) Zucker rats. The pattern of neuronal activation was studied by measuring the expression of the immediate-early gene c-fos. Expression of c-fos and CRH mRNA was determined by in situ hybridization histochemistry. In both lean and obese rats, one hour of refeeding led to a transient increase in c-fos mRNA levels which was detected in the paraventricular hypothalamic nucleus (PVH), the dorsomedial hypothalamic nucleus, the supraoptic nucleus, the paraventricular thalamic nucleus, the central nucleus of amygdala (CeA), the lateral and medial parabrachial nuclei, the nucleus of the solitary tract, and the area postrema. In addition, refeeding led to strong activation of the arginine-vasopressin neurons located in the magnocellular part of the PVH. Following 24 h of food deprivation, CRH expression in the parvocellular division of the PVH was significantly higher in obese rats compared to lean animals. During refeeding, PVH CRH mRNA levels in obese rats decreased to reach control values. The decrease in CRH expression in obese rats was accompanied by the alleviation of the hypercorticosteronemia that characterized obese Zucker rats. CRH mRNA levels in the central nucleus of the amygdala were significantly higher in lean rats than in obese animals, when the rats were fed ad libitum During food deprivation, CeA CRH mRNA levels decreased in lean rats and gradually returned to predeprivation values during refeeding. In refed obese rats, CeA levels of CRH mRNA were higher than those of ad libitum fed or food-deprived obese mutants. In the perifornical region of the lateral hypothalamic area (LHA), the expression of CRH mRNA rose significantly in response to refeeding in lean rats, but not in obese animals. Following the first hour of refeeding, the number of neurons expressing CRH mRNA in the LHA in lean rats almost doubled. The present results demonstrate that refeeding has a stimulating effect in obese Zucker rats in a pattern of activation similar to that seen in lean Fa/? rats. They also demonstrate differences in CRH expression between Fa/? and fa/fa rats after refeeding. The most apparent of these differences was seen in the lateral hypothalamus in which refeeding failed to up-regulate CRH expression in obese rats.

Animals↗

PubMed2002

Responses of adipose and muscle lipoprotein lipase to chronic infection and subsequent acute lipopolysaccharide challenge.

Infection of male Swiss Webster mice with Toxoplasma gondii or Neospora caninum leads to long-term alterations in energy balance. Following an initial 20 to 30% weight loss in all T. gondii-infected mice, half of the animals regain most of the lost weight (gainers), whereas the others maintain their low body weight (nongainers). Infection with N. caninum does not elicit weight loss. Lipoprotein lipase (LPL), the enzyme responsible for plasma triglyceride (TG) clearance and partitioning among tissues, is under tissue-specific modulation associated with energy balance. It is also a major determinant of infection-induced hypertriglyceridemia. This study aimed to assess the long-term modulation of adipose and muscle LPL activity in mice infected with T. gondii or N. caninum, to evaluate the effects of subsequent acute lipopolysaccharide (LPS) administration, and to relate LPL modulation in these conditions with infection-related changes in body weight gain. Twenty-eight days after infection, LPL activity in muscle of both gainer and nongainer T. gondii-infected mice was reduced by 40 to 50% compared with the levels in controls and N. caninum-infected mice, whereas LPL activity in adipose depots remained unchanged in all infected groups compared to the level in controls. LPS (from Escherichia coli, 100 ng/kg) injection induced a global reduction in adipose LPL in all groups, as assessed 90 min later. In both T. gondii-infected subgroups, muscle LPL was not further reduced by LPS treatment, whereas it was decreased by 40 to 50% in muscles of control and N. caninum-infected mice. Pre-LPS TG levels in plasma were similar in all groups. LPS greatly increased TG levels in plasma in both control and N. caninum-infected animals, whereas it did not alter those of T. gondii-infected gainer or nongainer animals. These results show that (i) independently of the extent of postinfection weight gain, long-term infection with T. gondii chronically reduces muscle LPL, which becomes unresponsive to acute endotoxemia; (ii) modulation of tissue LPL activity during chronic T. gondii infection favors TG partitioning towards adipose tissue; and (iii) skeletal muscle LPL is a key determinant of the acute response of triglyceridemia to LPS.

Adipose Tissue↗

PubMed2002

Leptin regulates appetite-related neuropeptides in the hypothalamus of developing rats without affecting food intake.

Leptin regulates food intake in adult mammals by stimulating hypothalamic anorexigenic pathways and inhibiting orexigenic ones. In developing rodents, fat stores are low, yet circulating leptin levels are high and do not appear to regulate food intake. We determined whether two appetite-related neuropeptides [neuropeptide Y (NPY) and proopiomelanocortin (POMC)] and food intake behavior are sensitive to leptin [3 mg/kg body weight (BW), ip] in neonates. We measured the effects of 1) acute leptin administration (3 mg/kg BW, ip, 3 h before testing) on food intake on postnatal day (PND) 5, 8, and 10; and 2) chronic leptin treatment (3 mg/kg BW, ip, daily PND3-PND10) on BW gain and fat pads weight on PND10. In addition to hypothalamic POMC and NPY expression, we determined the expression of suppressor of cytokine signaling-3, all subtypes of leptin receptors, and corticotropin-releasing factor receptor-2 mRNA in PND10 pups receiving either an acute (PND10) or a chronic (PND 3-10) leptin (3 mg/kg BW, ip) or vehicle treatment. Brains were removed 30 or 120 min after the last injection. Acute leptin administration did not affect food intake at any age tested. Chronic leptin treatment did not change BW but decreased fat pad weight significantly. In the arcuate nucleus (ARC), acute leptin increased SOCS-3 and POMC mRNA levels, but decreased NPY mRNA levels in the rostral part of ARC. Chronic leptin down-regulated all subtypes of leptin receptors mRNA and decreased NPY mRNA levels in the caudal ARC but had no further effect on POMC expression. Chronic leptin increased corticotropin-releasing factor receptor-2 mRNA levels in the ventromedial hypothalamus. We conclude that despite adult-like effects of leptin on POMC, NPY, and CRFR-2 expression in neonates, leptin does not regulate food intake during early development.

Adipose Tissue↗

PubMed2002

Interaction of CRH and energy balance in the modulation of brain stimulation reward.

The rewarding effect produced by electrical stimulation of some lateral hypothalamic sites is modulated by chronic food restriction and weight loss. The sensitivity of the rewarding effect to restriction predicts the modulation of brain stimulation reward (BSR) by the adiposity hormone, leptin. The present study examined the effect of corticotropin-releasing hormone (CRH) on the rewarding effect of stimulating restriction-sensitive and restriction-insensitive sites. Chronic food restriction reduced frequency thresholds for BSR in half of the subjects but had no effect in the others. CRH increased thresholds only in subjects in which the rewarding effect was insensitive to restriction. In contrast, frequency thresholds remained stable in nearly all rats with restriction-sensitive stimulation sites. These findings provide further evidence that sensitivity to food restriction is an important factor in determining the influence of hormones and neuropeptides on brain reward circuitry.

Animals↗

PubMedDate not supplied

COPD results in a reduction in UCP3 long mRNA and UCP3 protein content in types I and IIa skeletal muscle fibers.

PURPOSE: Findings recently have shown coupling protein-3 (UCP3) content to be decreased in the skeletal muscle of patients with chronic obstructive pulmonary disease (COPD). Uncoupling protein-3 mRNA exists as two isoforms: long (UCP3L) and short (UCP3S). The UCP3 protein is expressed the least in oxidative and the most in glycolytic muscle fibers. Levels of UCP3 have been associated positively with intramyocellular triglyceride (IMTG) contents in conditions of altered fatty acid metabolism. As a source for muscle free fatty acid metabolism, IMTG is decreased in COPD. The current study completely characterized all the parameters of UCP3 expression (ie, UCP3L and UCP3S mRNA expression in whole muscle samples) and UCP3 protein content as well as IMTG content in the different fiber types in patients with COPD and healthy control subjects. METHODS: Using real-time polymerase chain reaction, UCP3 gene expression was quantified. Skeletal muscle fiber type and UCP3 protein and IMTG content were measured using immunofluorescence and Oil red oil staining, respectively. RESULTS: The findings showed that UCP3L mRNA expression was 44% lower (P < .005) in the patients with COPD than in the control subjects, whereas the UCP3S mRNA content was similar in the two groups. As compared with control subjects, UCP3 protein content was decreased by 89% and 83% and the IMTG content by 64% and 54%, respectively, in types I and IIa fibers (P < .0167) of patients with COPD, whereas they were unchanged in IIx fibers. CONCLUSIONS: The reduced UCP3 and IMTG content in the more oxidative fibers may be linked to the altered muscle fatty acid metabolism associated with COPD. Further studies are required to determine the exact role and clinical relevance of the reduced UCP3 content in patients with COPD.

Aged↗