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Biomedical subjects

D Richard

Publications and source records attributed to D Richard.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effect of leptin on energy balance does not require the presence of intact adrenals.

The present study was conducted to assess the effects of leptin on food intake and energy balance in the presence or absence of corticosterone. Three cohorts of C57BL/6 mice differing in their corticosterone status [nonadrenalectomized (intact), adrenalectomized (ADX), and ADX with corticosterone replacement] were infused with either saline or leptin at a dose of 150 microg . kg-1 . day-1. Throughout the study, mice had free access to both a high-starch and a high-fat diet. At the end of the experimental period, mice were decapitated and their carcasses were processed for the determination of energy, protein, and lipid contents. Leptin significantly reduced body gains in weight, fat, and energy, whereas corticosterone therapy significantly promoted all of these gains. Leptin and ADX significantly reduced food intake and gross energetic efficiency, whereas corticosterone therapy significantly increased these variables. The effects of leptin, ADX, and corticosterone on food intake were accounted for by changes in the intake of the high-fat diet. Leptin also attenuated the preference for fat that developed quickly in mice simultaneously exposed to the high-starch and high-fat regimen. Altogether, the results of this study 1) emphasize the abilities of leptin and corticosterone to, respectively, decrease and increase energy deposition and ingestion of fat, 2) do not substantiate any leptin-corticosterone interaction in the regulation of energy balance, and 3) demonstrate that leptin can produce its effect on energy and fat gains in the absence of an intact hypothalamic-pituitary-adrenal axis.

Adipose Tissue↗
PubMed1998

Effects of leptin on corticotropin-releasing factor (CRF) synthesis and CRF neuron activation in the paraventricular hypothalamic nucleus of obese (ob/ob) mice.

The effects of leptin on the levels of CRF messenger RNA (mRNA) in the paraventricular hypothalamic nucleus (PVN), on the activation of the PVN CRF cells, and on the plasma levels of corticosterone were investigated in lean (+/?) and obese (ob/ob) C57BL/6J male mice. Murine leptin was s.c. infused using osmotic minipumps. The treatment period extended to 7 days, and the daily dose of leptin delivered was 100 microg/kg. The mice were killed either in a fed state or following 24 h of total food deprivation. The starvation paradigm was employed to enhance the activity of the hypothalamic-pituitary-adrenal axis in obese mice. In situ hybridization histochemistry was performed to determine the PVN levels of CRF mRNA and the arcuate nucleus levels of neuropeptide Y mRNA. The activity of the PVN CRF cells was estimated from the number of PVN cells colocalizing CRF mRNA and the protein Fos. Leptin led to a reduction in body weight gain and fat deposition. These effects were seen in both +/? and ob/ob mice and were observed to be particularly striking in obese mutants, in which leptin also caused an important reduction in food intake. Leptin also was found to affect plasma levels of corticosterone. It lowered the high corticosterone levels of obese mutants, an effect that appeared more evident in food-deprived than in fed mice. Finally, leptin prevented the induction of CRF synthesis in the PVN and the activation of the PVN CRF neurons observed in food-deprived ob/ob mice and hindered the elevation of arcuate nucleus neuropeptide Y synthesis in ob/ob mice. Together these results suggest a role for leptin in the excessive response of the hypophysiotropic CRF system of the ob/ob mouse.

Adipose Tissue↗
PubMed1998

Increased fat intake during lactation modifies hypothalamic-pituitary-adrenal responsiveness in developing rat pups: a possible role for leptin.

High fat feeding reportedly enhances hypothalamus-pituitary-adrenal (HPA) responses to stress in adult rats. The present study tested whether elevated fat intake during suckling could have short and/or long lasting consequences on HPA regulation in the offspring. Mothers were fed either a control (C; 5% fat) or high fat (HF; 20% fat) diet during the last week of gestation and throughout lactation. After weaning (day 21), pups from C and HF mothers were fed a chow diet. Offspring from both C- and HF-fed mothers were tested for ACTH and corticosterone responses to stress on postnatal days 10 and 35. We found that HF feeding produced higher lipid levels in the milk of HF compared with C lactating rat dams and that offspring of these mothers had significantly increased retroperitoneal fat pad weight and relative adipose mass on day 21 as well as elevated plasma leptin levels on days 10 and 21 of age. After weaning, pups from the HF mothers had lower plasma leptin levels than those from C mothers. Maternal dietary fat affected HPA responsiveness in the offspring in an age-related manner. Neonatal pups (day 10) from the HF mothers exhibited a reduction in the ACTH and corticosterone responses to ether stress. However, in 35-day-old offspring from HF-fed dams, stress-induced ACTH secretion was increased compared with that in pups from the C-fed mothers. These results demonstrate that maternal diet and increased fat intake through the milk are important regulators of HPA responsiveness in neonates and prepubertal rats. During neonatal life, the blunted stress responsiveness seen with elevated fat intake and the resulting high leptin levels might protect the pups from excessive HPA activation. After removal of the maternal dietary influence and reduced leptin levels, enhanced ACTH stress responses are observed as in adult rats fed a HF diet. Because of the inverse relationship between plasma levels of leptin and HPA responses in pups, the possibility exists that the effects of the HF diet on stress responsiveness are mediated by changes in leptin exposure during development.

Adipose Tissue↗
PubMed1998

Leptin and corticosterone have opposite effects on food intake and the expression of UCP1 mRNA in brown adipose tissue of lep(ob)/lep(ob) mice.

The present study was conducted to assess the interaction effect of leptin and corticosterone on food intake and the expression of uncoupling protein 1 (UCP1) mRNA in interscapular brown adipose tissue (IBAT). To this end, a 3 x 3 factorial experiment was designed in which adrenalectomized (ADX) lep(ob)/lep(ob) mice were subjected to three doses of corticosterone and three doses of leptin. The results confirm the anorectic and orexigenic effects of leptin and corticosterone, respectively. The results also emphasize the abilities of leptin and corticosterone to respectively increase and reduce the expression of UCP1 mRNA in IBAT. The effects of leptin and corticosterone on food intake and the expression of UCP1 mRNA translated into effects on body weight and body composition; leptin reduced body weight and corticosterone increased the weight of IBAT. The present results do not provide evidence for leptin-corticosterone interactions in the control of food intake and thermogenesis. Corticosterone increased food intake and reduced the expression of IBAT UCP1 regardless of the leptin status, and leptin reduced food intake and induced the expression of IBAT UCP1 independently of the corticosterone levels.

Adipose Tissue, Brown↗
PubMed1997

The food-hoarding threshold is not raised by acute intraventricular NPY in male rats.

We studied the influence of acute intracerebroventricular (i.c.v.) NPY on the relation existing in the rat between food-hoarding behavior and the body weight of the animals. Six male rats were trained to feed every day from 1000 to 1200 h. Then, their threshold for the onset of food hoarding was measured from the intercept of the regression line relating the food hoarded during meal time (Y axis) to the body weight (X axis). Thirty minutes before the hoarding session, the rats were injected i.c.v. with either 4 micrograms of NPY or saline control. The mean threshold for food hoarding was not modified after NPY. Mean food intake during the hoarding sessions was also unchanged. These results suggest that intracerebral NPY at 4 micrograms did not acutely alter the set-point for body weight regulation.

Animals↗
PubMed1997

Neuronal activation of the hypothalamic magnocellular system in response to oropharyngeal stimuli in the rat.

The present study was designed to delineate the neuronal site, the nature, and the gastrointestinal origin of the stimulation of the hypothalamic magnocellular system induced by the ingestion of sweetened condensed milk. Concomitant localization of the c-fos protein (Fos) with either arginine-vasopressin (AVP) mRNA or oxytocin (OT) mRNA in the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON) revealed that the hypothalamic neurons containing AVP and OT were activated following ingestion of sweetened condensed milk. Expression of c-fos mRNA was also determined in rats implanted with a gastric cannula that allowed for real, sham, and gastric feeding of sweetened condensed milk. The results provide evidence that the stimulation of the PVH and SON induced by sweetened condensed milk originate from oropharyngeal stimuli. Indeed, in real-and sham-fed rats, the postprandial levels of c-fos mRNA in the PVH and SON were significantly higher than the preprandial values, whereas there was no early postprandial rise in c-fos mRNA levels within the magnocellular division of the PVH and SON after gastric feeding. The results of this study also suggested that the stimulation of the PVH and SON induced by sweetened condensed milk was related to the hypertonicity of the milk, indeed, ingestion of an hypertonic solution of sucrose with a carbohydrate content close to that of sweetened condensed milk led to a stimulation of the PVH and SON that was comparable to that induced by the milk, whereas ingestion of an isotonic solution of sucrose did not trigger any significant activation of the PVH and SON. Taken together, the present results indicate that magnocellular neurosecretory neurons are sensitive to oropharyngeal stimuli and further support the view of the existence of oropharyngeal osmoreceptors.

Animals↗
PubMed1997

Interaction of corticosterone and gonadal steroids on lipid deposition in the female rat.

The present study was designed to evaluate the interaction of corticosterone (CORT) and female gonadal steroids on energy balance and lipid metabolism. To this end, a 2 x 4 factorial experiment was carried out in which two cohorts of rats differing in their ovary status [OV status: intact (INT) and ovariectomy (OVX)] were each divided into four groups defined by their CORT status [CORT status: nonadrenalectomized (non-ADX), ADX without CORT replacement (placebo subcutaneous pellet), ADX with low-dose CORT replacement, and ADX with high-dose CORT replacement]. After 3 wk of treatment and a 12-h fast, rats were killed and their carcasses analyzed for energy (lipid and protein) content. In addition, indexes of endogenous triglyceride (TRIG) production (liver TRIG content), transport into plasma (triglyceridemia), and incorporation into fat stores [lipoprotein lipase (LPL) activity in adipose tissue (AT)] were assessed. OV and CORT status interacted on body weight gain, total energy, and fat gains. The interactions arose from the fact that the twofold increase in these variables brought on by OVX was abolished by ADX and restored by CORT replacement. Although in ADX groups there was a dose-related restoration of total energy and fat gain by CORT replacement in both INT and OVX cohorts, the impact thereupon of OVX observed in the non-ADX group reappeared only in ADX animals receiving the high dose of CORT. Protein gain was increased by OVX solely in non-ADX rats, whereas the high dose of CORT prevented any net protein gain independently of the OV status. Consistent with treatment effects on total body fat gain, OVX resulted in an increase in liver TRIG content, AT weight, AT LPL activity, and plasma insulin. All these effects of OVX were abolished by ADX and restored by the high dose of CORT. Plasma TRIG were unaffected by OV status but were highly responsive to CORT status. All treatment effects were highly correlated with cumulative food intake. This study shows that the presence of CORT is required for OVX to exert its action on global energy balance and the concomitant, closely integrated adaptations of lipid metabolism.

Adipose Tissue↗
PubMed1997

Involvement of the medial preoptic area in the anorectic action of estrogens.

The implication of the medial preoptic area (MPOA) as a site for estrogen in the regulation of energy balance was investigated. Food intake, O2 consumption (VO2), and CO2 production were measured in ovariectomized rats injected with estradiol (E2) in the medial preoptic nucleus (MPN). Moreover, knowing the potential for corticotropin-releasing factor (CRF) in the anorectic effects of estrogens, we identified estrogen receptors (ER) colocalized in CRF-containing cells of the MPOA and how MPN injections of CRF compared with estrogen injections with respect to VO2 and the VO2-to-CO2 production ratio (respiratory quotient RQ). These energy balance measurements after the injections of four different doses of E2 or CRF were carried out in meal-fed rats chronically implanted with a guide cannula targeted to the MPN. The identification of cells colocalizing ER and CRF was determined using a double-immunostaining procedure revealing ER and CRF immunoreactivities with two different couplers. The injection of E2 into the MPN induced a dose-dependent reduction in food intake, whereas it did not affect VO2 or RQ. Conversely, the injection of CRF into the MPN had no effect on food intake but increased VO2 and decreased RQ. The colocalization of ER and CRF immunoreactivities was found in the MPOA and adjacent regions of the bed nucleus of the stria terminalis. In conclusion, the results of this study provide evidence that the MPOA may represent a potential site for the anorectic effects of E2. Furthermore, the presence of ER and CRF in neurons of the MPOA and adjacent areas suggests a direct interaction between estrogens and the CRF system in the MPOA that is consistent with a role for CRF in the anorectic effects of estrogens. Finally, the results of this study indicate that the effects of a CRF injection into the MPOA differ from those of estrogens, suggesting that if CRF neurons are involved in the anorectic effect of estrogens they likely exert their action outside the MPOA.

Animals↗
PubMed1997

Functional activation of CRH neurons and expression of the genes encoding CRH and its receptors in food-deprived lean (Fa/?) and obese (fa/fa) Zucker rats.

The time course of the action of food deprivation on the functional activation of corticotropin-releasing hormone (CRH) neurons and on the expression of the genes encoding CRH and its receptors of type 1 (CRH1-R) and 2alpha (CRH2-R) in the brain were assessed in lean (Fa/?) and obese (fa/fa) Zucker rats. Fa/? and fa/fa rats were assigned to food deprivation periods of 0, 3, 6, 12, and 24 h. Measurements of Fos immunoreactivity and CRH mRNA were carried out on the same brain sections to assess the state of activation of CRH neurons. In situ hybridization histochemistry was employed to measure the mRNAs encoding CRH and its receptors. In fa/fa rats, food deprivation induced a rapid expression of Fos in CRH cells of several brain regions that include the paraventricular hypothalamic nucleus (PVN), the bed nucleus of the stria terminalis (BNST), the anterodorsal preoptic nucleus, the medial preoptic nucleus, the substantia innominata and Barrington's nucleus. The colocalization of Fos immunoreactivity and CRH mRNA was particularly noticeable in the PVN of fa/fa rats, where the majority of the CRH cells of the parvocellular division of the nucleus displayed Fos-positive nuclei, 12 h after the onset of fasting. In obese rats, food deprivation also produced an increase in the CRH mRNA levels in the BNST as well as high and low expressions of the CRH1-R in, respectively, the PVN and the anterior lobe of the pituitary. The expression of CRH1-R in the PVN of obese rats occurred 12 h after the onset of the deprivation. In Fa/? rats, food deprivation induced no marked activation of the CRH cells, a slow decrease in the CRH mRNA levels in the BNST and the central nucleus of the amygdala, and a gradual decrease in the expression of CRH2-R gene in the ventromedial hypothalamic nucleus. These results demonstrate that food deprivation is capable of generating in obese Zucker rats a stress-like response that translates into a particularly striking activation of the hypothalamic-pituitary-adrenal axis. This response contrasts with that observed in Fa/? rats, in which the action of food deprivation on the CRH system seems more compatible with the known effects of CRH in the regulation of energy balance.

Animals↗
PubMed1996

Atrial natriuretic peptide modulates synaptic transmission from osmoreceptor afferents to the supraoptic nucleus.

Atrial natriuretic peptide (ANP) and its receptors are present in hypothalamic nuclei containing the magnocellular neurosecretory cells (MNCs), which release vasopressin and oxytocin. In the rat, intracerebroventricular injections of ANP inhibit the release of both hormones in response to hypertonicity. Although these findings suggest a role for endogenous ANP in the central control of fluid balance, cellular mechanisms underlying the modulatory actions of ANP are unknown. We therefore examined the effects of ANP on the osmoresponsiveness of MNCs impaled in rat hypothalamic explants. Applications of ANP (75-150 nM) over the supraoptic nucleus did not affect depolarizing responses to local hypertonicity, but they reversibly abolished the synaptic excitation of MNCs after hypertonic stimulation of the organum vasculosum laminae terminalis (OVLT). These effects were associated with decreased spontaneous EPSP (sEPSP) amplitude rather than with changes in sEPSP frequency. Accordingly, application of ANP reduced the amplitude of glutamatergic EPSPs evoked by electrical stimulation of the OVLT (IC50 approximately 3 nM). The inhibitory effects of ANP on EPSP amplitude were mimicked by application of 3'-5'-dibutyryl cGMP, consistent with the guanylate cyclase activity of natriuretic peptide receptors. Although depolarizing responses of MNCs to ionotropic glutamate receptor agonists were unaffected by ANP, the peptide reversibly enhanced paired-pulse facilitation of electrically evoked EPSPs. These results indicate that centrally released ANP may inhibit osmotically evoked neurohypophysial hormone release through presynaptic inhibition of glutamate release from osmoreceptor afferents derived from the OVLT.

Animals↗
PubMed1996

Helium Isotopic Evidence for a Lower Mantle Component in Depleted Archean Komatiite

Archean magnesium-rich komatiites require hot and presumably deep mantle sources, but their trace-element composition and radiogenic isotope composition are similar to those of modern mid-ocean ridge basalts, which originate in the upper mantle. The isotopic composition of helium extracted by sequential crushing of fresh olivines separated from two Archean and one mid-Proterozoic komatiites varies over three orders of magnitude, between a radiogenic end-member rich in helium-4 and a component rich in helium-3. Such helium-3 enrichment suggests the presence of a lower mantle component in Archean komatiites.

Journal Article↗
PubMed1996

The nature of the ponderostat: Hervey's hypothesis revived.

In 1969, Hervey hypothesized the long-term stability of body weight is actually mediated through the regulation of blood steroid concentration. We suggest that glucocorticoids are the regulated variable the concentrations of which entails bodyweight stability. A descriptive model of this regulation is proposed. Because steroids are soluble in lipids, it follows that their concentrations in the body depend in part of the volume of lipids stored. Low fat stores increase the glucocorticoid concentration in the blood, and conversely high fat stores lower the glucocorticoid concentration. Body weight could thus be the end product of the glucocorticoid levels. The set-point for body weight would be adjusted by intracerebral CRH.

Animals↗
PubMed1996

Fenfluramine-induced activation of the immediate-early gene c-fos in the striatum: possible interaction between serotonin and dopamine.

DL-Fenfluramine, a serotonin (5-HT) releasing agent, induces rapid expression of Fos-like immunoreactivity (Fos-LI) in the striatum as well as in other brain structures receiving a dense 5-HT innervation. Fenfluramine-induced Fos-LI expression in the striatum may result directly from the activation of 5-HT receptors or may be the result of interactions between dopamine (DA) and 5-HT neurotransmitter systems. To discriminate between these two possibilities, various groups of rats were pretreated with different 5-HT antagonists or a DA D1 antagonist, 20 min before fenfluramine administration. Animals were killed 60 min later. In the striatum, fenfluramine-induced expression of Fos-LI was almost completely blocked by SCH 23390, methysergide and S(-)-propranolol. The immediate-early gene response to fenfluramine was only slightly affected by pretreatment with the 5-HT2A/2C antagonist ritanserin. Fenfluramine was also administered to sham-operated and to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. In the 6-OHDA-lesioned rats, fen-fluramine-induced Fos-LI was decreased by 60% on the DA denervated side compared to the intact side and to sham-operated rats. To further probe the possibility of a direct activation of Fos-LI by 5-HT receptor subtypes, we evaluated the expression of Fos-LI after the administration of different 5-HT agonists. Our results demonstrate that neither 8-OH-DPAT, CGS-12066B, RU 24969 nor phenyl-biguanide was able to reproduce the effects of fenfluramine. Only a high dose of DOI (8.5 mg/kg) produced a moderate expression of Fos-LI in the dorsomedial part of the striatum. This contrasted with the Fos-LI expression in other brain areas where 8-OH-DPAT and DOI (2.5 and 8.5 mg/kg) reproduced the effects of the 5-HT releasing agent. Our results suggest that the release of 5-HT by fenfluramine induced Fos-LI expression predominantly in a striatal region related to associative functions and, that this c-fos response may be under the control of both 5-HT and DA. Moreover, the mechanism by which fenfluramine induces c-fos expression in the striatum differs from other brain regions.

Animals↗
PubMed1996

Mecamylamine-induced impairment of acquisition and retrieval of olfactory conditioning in the honeybee.

Mecamylamine, a nicotinic receptor antagonist, was injected into the honeybee brain haemolymph. The effects of the drug were investigated on Pavlovian conditioning of the proboscis extension reflex. The conditioned response was acquired after a one-trial learning session, consisting of an olfactory-conditioned stimulus combined with a gustatory antennal unconditioned stimulus. The drug was injected at different times before or after the learning session in order to dissociate its effects on acquisition, consolidation and retrieval processes. The performance was evaluated in short-delayed recall tasks. To control potential effects on sensory-motor activity, the effects of the drug were also investigated on sensory processes (through olfactory and gustatory functions) and on motor processes of proboscis extension. The results of conditioning experiments showed that pretrial injection induced a decrease of retention performance 1 h after the learning trial. Mecamylamine injected 20 min after the learning session induced a time-dependent impairment of retention performance, as has been shown by the performance level registered from 10 to 80 min after injection. A 5-min post-trial injection had no effect on retention performance. Control experiments did not reveal any effect of mecamylamine on the response reflex of proboscis extension and on responsiveness to olfactory stimuli (geraniol, lavender and vanillin). The absence of effects on sensory perception combined with the amnestic effect induced by pre- or late post-trial injections lead us to conclude that mecamylamine specially impaired acquisition and retrieval processes. The involvement of nicotinic-like receptors in these processes is discussed.

Animals↗
PubMed1996

Age of wife as a major determinant of male-to-female transmission of HIV-2 infection: a community study from rural West Africa.

OBJECTIVE: To examine whether proviral load is important for transmission between spouses, since we have previously found that the proviral load of HIV-2 predicts the severity of infection. DESIGN: Proviral load was examined in 121 HIV-2-infected adults in a rural area of Guinea-Bissau. For the 68 subjects who had a spouse of known HIV status the risk of the spouse being infected was examined. METHODS: Statistical methods for dependent data were used, because several couples were polygamous. RESULTS: Twenty-seven HIV-2-infected men had 52 current wives of whom 17 (33%) were HIV-2-seropositive. Forty-one HIV-2-infected women had 36 current husbands of known HIV serostatus; nine (25%) were HIV-2-positive. In univariate analyses, concordance of female partners of HIV-2-infected men increased with a previous history of prostitution, age of wife, lack of age difference between the spouses, number of previous husbands, number of wives of the man, and the proviral load. The only significant predictor of concordance in multivariate analyses when wives with a history of prostitution were excluded was an age of 45 years or older [odds ratio (OR), 8.68; 95% confidence interval (CI), 2.34-32.22]. This tendency was not explained by the length of current marriage. Although husbands with a high proviral load were more likely to have concordant spouses than those with a low proviral load (< 20 copies/10(5) CD4 cells), this association was not statistically significant (OR, 2.59; 95% CI, 0.90-7.46). Among spouses of HIV-2-infected women, none of the examined factors, including previous prostitution or proviral load in the woman, predicted whether the husband was HIV-2-infected. CONCLUSIONS: Women appear to be more susceptible to HIV-2 infection after 40-45 years of age. The apparent change in susceptibility may be a major reason for the distinctive age pattern of HIV-2 infection observed in West Africa.

Adolescent↗