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J G Mercer

Publications and source records attributed to J G Mercer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Association of leptin receptor (OB-Rb), NPY and GLP-1 gene expression in the ovine and murine brainstem.

Appetite-related neuropeptide systems have not been studied extensively in the ruminant, although there have been a number of recent studies of the hypothalamus. Since some leptin signaling is integrated in the rodent brainstem, and leptin modulates neuropeptidergic activity, we now describe leptin receptor (long splice variant, OB-Rb), neuropeptide Y (NPY) and glucagon-like peptide-1 (GLP-1) gene expression in the ovine brainstem. Leptin receptor mRNA was localized to the spinal trigeminal tract and nucleus, nucleus of the solitary tract (NTS), area postrema and dorsal motor nucleus of the vagus. NPY gene expression was abundant in the ovine medulla, occurring in two bilateral 'bands' that encompassed the NTS region and ran ventrolaterally. GLP-1 mRNA was confined largely to the NTS. The distribution of OB-Rb mRNA overlapped with that of NPY and GLP-1 gene expression, suggesting the possibility of interaction between leptin and these brainstem neuropeptide systems. However, in an extension of earlier work, co-expression studies in the murine brainstem revealed only a small number of neurons that expressed both NPY and leptin receptor mRNA, despite the widespread and abundant expression of the former. Thus the majority of NPY synthesis in the brainstem may not be directly regulated by leptin. The sheep brainstem had similar anatomical distribution of OB-Rb, NPY and GLP-1 gene expression to the rodent, consistent with a role for this region in peripheral leptin feedback signaling and brainstem-hypothalamo communication.

Animals↗
PubMed1998

Hypothalamic neuropeptide Y content and mRNA expression in weanling rats subjected to dietary manipulations during fetal and neonatal life.

Hypothalamic neuropeptide Y (NPY) is present very early during the fetal life and is rapidly functional in the regulation of feeding behavior after birth. In the present experiment, we tried to determine the influence that the diet type ingested by dams during gestation and lactation would have on the growth and hypothalamic and pancreatic peptides of their progeny immediately after weaning. The dams were fed on either a high-carbohydrate (HC), a high-fat (HF) or a control diet ad libitum. At 3 days of age, the HC pups weighed significantly more than the two other groups (P < 0.02 vs. C and P < 0.002 vs. HF). At weaning, the HF rats were significantly lighter than the two other groups (P < 0.001). Food intake was significantly lower in the HF rats than in the two other groups 3 days (P < 0.002) and 5 days after weaning (P < 0.02). Plasma glucose of the HF rats was significantly lower than that of the control rats (P < 0.05) and of the HC rats (P < 0.01). Immunoreactive insulin in the HF rats was also significantly lower than that in the control rats (-53%; P < 0.001) and in the HC rats (-47%; P < 0.001). NPY content and mRNA expression in the arcuate nucleus were not significantly different between the three groups. NPY concentration only varied in the ventromedian nucleus. In the control rats, it was significantly lower than that of the HC rats (-35%; P < 0.01) and that of the HF rats (-32%; P < 0.002). These data demonstrated that the regulatory mechanisms of feeding behavior in offspring are completely and differentially modified by the macronutrient content of the diets ingested by their mother. Both peripheral and central mediators were strongly implicated. These modifications could have long-term repercussions on body weight and composition.

Animals↗
PubMed1998

Leptin (ob) mRNA and hypothalamic NPY in food-deprived/refed Syrian hamsters.

Food deprivation in the laboratory rat decreases plasma leptin and insulin, elevates glucocorticoid concentration, and increases the activity of the neuropeptide Y (NPY) system and feeding drive. In contrast, Syrian hamsters fail to modify feeding behaviour in response to various food scarcity paradigms. Two components of the neuroendocrine-hormonal response to food deprivation, adipose tissue-derived leptin and hypothalamic NPY, are investigated in the Syrian hamster. ob (leptin) mRNA was less abundant in subcutaneous than abdominal adipose tissue, but not to the extent observed in other rodents. Food deprivation for 48 h reduced ob mRNA in inguinal and retroperitoneal white adipose tissue; gene expression was partially restored by refeeding. In contrast, in epididymal fat there was no effect on ob mRNA. NPY concentrations in hypothalamic nuclei were also unaffected by feeding state. The predicted amino acid sequence of leptin from the Syrian hamster was over 90% homologous with Djungarian hamster and mouse sequences, and the leptin receptor gene (OB-R), and specifically the long intracellular splice variant, OB-Rb, was expressed in the same forebrain and hypothalamic regions that have been described in laboratory mice and rats, including hypothalamic arcuate, dorsomedial, and ventromedial nuclei. The failure of food deprivation to affect NPY and feeding behaviour in Syrian hamsters is unlikely to be due to defects in the leptin system, although there may be region-specific differences in the regulation of leptin signaling in laboratory rats and Syrian hamsters.

Adipose Tissue↗
PubMed1998

Regulation of appetite and body weight in seasonal mammals.

As models of physiological regulation of body weight, adiposity and appetite, seasonal mammals offer unique opportunities for manipulating fundamental regulatory processes that may not be available in the more frequently-studied laboratory rodents. Seasonal weight and intake cycles are anticipatory rather than reactive in nature, being manifest despite the availability of adlibitum supplies of food. They are exhibited despite all other environmental variables being held constant, and are reversible. Appropriate body weight appears to be a sliding set point in many seasonal mammals, which can move in either direction, largely independently of age. While few data are available other than from rats and mice, there appears to be a strong commonality of central neuroendocrine and peripheral signalling systems between seasonal and non-seasonal mammals, although the conditions under which endogenous regulatory pathways are activated may differ significantly between species. Peripheral and central signalling systems implicated in the regulation of appetite and body weight may be modulated during seasonal transitions. Discussion will concentrate on hypothalamic neuropeptides, gastrointestinal satiety peptides, the recently-described peptide, leptin, that is secreted by adipose tissue, and the interactions between these regulatory components.

Animals↗
PubMed1998

Hormonal and neuroendocrine regulation of energy balance--the role of leptin.

A new dimension to the regulation of energy balance has come from the identification of the ob (obese) gene and its protein product, leptin. Leptin is produced primarily in white adipose tissue, but synthesis also occurs in brown fat and the placenta. Several physiological functions have been described for leptin the inhibition of food intake, the stimulation/maintenance of energy expenditure, as a signal of energy reserves to the reproductive system, and as a factor in haematopoiesis. The production of leptin by white fat is influenced by a number of factors, including insulin and glucocorticoids (which are stimulatory), and fasting, cold exposure and beta-adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production is envisaged for the sympathetic nervous system, operating through beta 3-adrenoceptors. The leptin receptor gene is expressed in a wide range of tissues, and several splice variants are evident. A long form variant (Ob-Rb) with an intracellular signalling domain is found particularly in the hypothalamus. Leptin exerts its central effects through neuropeptide Y, and through the glucagon-like peptide-1 and melanocortin systems, but it may also interact with other neuroendocrine pathways. The role and function of the leptin system in agricultural animals has not been established, but it offers a potential new target for the manipulation of body fat.

Animals↗
PubMed1998

Localization of leptin receptor (Ob-R) messenger ribonucleic acid in the rodent hindbrain.

The behavioral and neuroendocrine effects of the adipose tissue-derived circulating protein, leptin, appear to be mediated by the hypothalamus. We have investigated whether the leptin receptor gene is expressed in hindbrain regions known to be involved in the processing of satiety and energetic signals of peripheral origin. In the mouse, gene expression was detected in the nucleus of the solitary tract, lateral parabrachial nucleus, and medullary reticular nucleus and diffusely elsewhere by in situ hybridization. Receptor messenger RNA in these neuronal areas consisted largely, if not exclusively, of the long splice variant, Ob-Rb. Presumed short receptor splice variants were abundantly expressed in the leptomeninges and the choroid plexus of the fourth ventricle. Similar levels of leptin receptor gene expression were present in the hindbrain of lean and obese (ob/ob) mice. The leptin receptor gene was expressed comparatively weakly in the nucleus of the solitary tract of the rat and was not detectable in the lateral parabrachial nucleus. However, by contrast with the mouse, a high level of receptor gene expression was observed in the cerebellum of the rat. A number of rodent hindbrain sites expressing the leptin receptor gene are activated by circulating leptin and may form a monitoring/signaling pathway to complement more direct hypothalamic interactions.

Animals↗
PubMed1997

Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta.

Leptin is a 167-aa protein that is secreted from adipose tissue and is important in the regulation of energy balance. It also functions in hematopoiesis and reproduction. To assess whether leptin is involved in fetal growth and development we have examined the distribution of mRNAs encoding leptin and the leptin receptor (which has at least six splice variants) in the 14.5-day postcoitus mouse fetus and in the placenta using reverse transcription-PCR and in situ hybridization. High levels of gene expression for leptin, the leptin receptor, and the long splice variant of the leptin receptor with an intracellular signaling domain were observed in the placenta, fetal cartilage/bone, and hair follicles. Receptor expression also was detected in the lung, as well as the leptomeninges and choroid plexus of the fetal brain. Western blotting and immunocytochemistry, using specific antibodies, demonstrated the presence of leptin and leptin receptor protein in these tissues. These results suggest that leptin may play a role in the growth and development of the fetus, both through placental and fetal expression of the leptin and leptin receptor genes. In the fetus, leptin may be multifunctional and have both paracrine and endocrine effects.

Animals↗
PubMed1997

Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents.

The adipose tissue hormone, leptin, and the neuropeptide glucagon-like peptide-1 (7-36) amide (GLP-1) both reduce food intake and body weight in rodents. Using dual in situ hybridization, long isoform leptin receptor (OB-Rb) was localized to GLP-1 neurons originating in the nucleus of the solitary tract. ICV injection of the specific GLP-1 receptor antagonist, exendin(9-39), at the onset of dark phase, did not affect feeding in saline pre-treated controls, but blocked the reduction in food intake and body weight of leptin pre-treated rats. These findings suggest that GLP-1 neurons are a potential target for leptin in its control of feeding.

Animals↗
PubMed1997

Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization.

Expression of leptin receptor splice variants, including the long form variant (Ob-Rb), has been examined in murine peripheral tissues. RT-PCR indicates that the leptin receptor, Ob-R, and in particular the Ob-Ra splice variant are expressed in a wide range of tissues. Expression of the Ob-R receptor was localized by in situ hybridization to specific sites in the spleen, testes, kidney, liver, lung, and adrenal. However, the long form leptin receptor, Ob-Rb, was only expressed at significant levels in the medulla of the adrenal and the inner zone of the medulla of the kidney. The specific sites of expression of different splice variants within peripheral tissues has important implications with regard to the function of leptin.

Animals↗
PubMed1997

Regulation of leptin receptor and NPY gene expression in hypothalamus of leptin-treated obese (ob/ob) and cold-exposed lean mice.

Leptin receptor gene expression has been measured in arcuate and ventromedial hypothalamic nuclei. Receptor mRNA in both hypothalamic areas was higher in obese mice than in lean littermates. Twice daily leptin administration for 7 days profoundly affected food intake, reduced leptin receptor mRNA in the arcuate nucleus, and had a similar effect on neuropeptide Y gene expression. A single leptin injection was ineffective. Exposure of lean mice to cold for 24 h caused an induction of leptin receptor and NPY mRNA which was normalized when animals were returned to the warm. Regulation of receptor gene expression may be an important component in the reading of the leptin signal.

Acclimatization↗
PubMed1997

Melatonin receptors in the brain and pituitary gland of hypothalamo-pituitary disconnected Soay rams.

In Soay rams in which the pituitary gland has been surgically separated from the hypothalamus, blood prolactin concentrations vary in response to changes in photoperiod and the administration of melatonin, as in intact animals, providing evidence that melatonin acts within the pituitary gland to control prolactin secretion. In this study the presence of potentially functional melatonin receptors in the pars tuberalis and zona tuberalis (PT/ZT) of hypothalamo-pituitary disconnected (HPD) Soay rams is confirmed using both in vitro autoradiography with the ligand 2-(125I)-iodomelatonin and in situ hybridization for the melatonin receptor. There was no effect of the HPD operation on the pattern and quantity of 2-(125I)iodomelatonin binding in the brain demonstrating that this binding is independent of hypothalamic regulation. The possibility that melatonin may control prolactin secretion directly via specific receptors on lactotrophs was investigated using dual in situ hybridization with a (35S) labelled probe for the ovine melatonin receptor (Mel 1a(b)) and a Digoxigenin labelled probe for ovine prolactin. Melatonin receptor gene expression was observed in the PT/ZT in both intact and HPD rams, however, there was no colocalization with prolactin gene expression; only in the ZT was there a close association between cells expressing the melatonin receptor and lactotrophs. The results provide strong support for the view that melatonin acts via the PT/ZT to mediate the effects of photoperiod on the seasonal cycle in prolactin secretion.

Animals↗
PubMed1997

Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF mRNA in Djungarian hamsters.

The effect of food deprivation on hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) gene expression in the Djungarian hamster was quantified by in situ hybridization. Hamsters housed in short days (SD) for 18 wk decreased body weight by 40% and exhibited 200% increases in both NPY and CRF mRNA when deprived of food for 24 h. Prior gonadectomy in long days (LD) affected neither basal gene expression nor the induction of gene expression by food deprivation. Gene expression in juvenile LD hamsters similar in body weight to SD animals was relatively insensitive to food deprivation of either 24- or 48-h duration or to subsequent refeeding. In juvenile hamsters, food deprivation for 24 but not 48 h decreased ob (obese) gene expression in inguinal but not epididymal white adipose tissue; ob mRNA levels were restored by refeeding. All food-deprived hamsters had reduced plasma insulin concentrations, but plasma cortisol was only elevated in SD food-deprived animals. NPY gene expression was also increased after daily dexamethasone injections in adult LD hamsters. These results suggest that the neuroendocrine consequences of food deprivation in SD Djungarian hamsters are determined by some factor other than absolute body mass such as the size of adipose tissue reserves.

Animal Feed↗
PubMed1997

Effect of chronic food restriction on pulsatile luteinizing hormone secretion and hypothalamic neuropeptide Y gene expression in castrate male sheep.

Castrate male sheep (wethers, average liveweight 38 +/- 0.6 kg) were given one of the following diets for 10 weeks followed by euthanasia (n = 8/group): high-energy high-protein providing 1-5 times the energy required to maintain liveweight (maintenance) (group 1.5 M), low-energy low-protein at 0.5 maintenance (0.5 M), or low-energy high-protein at 0.5 maintenance (0.5 M + P). 1.5 M wethers gained 22% liveweight whereas 0.5 M and 0.5 M + P wethers lost 18 and 13% liveweight respectively. Relative to the 1.5 M group, the 0.5 M and 0.5 M + P groups had similar plasma concentrations of glucose and cortisol throughout, but elevated non-esterified fatty acids (P < 0.001) and reduced IGF-I and insulin (P < 0.05, 0.01 or 0.001) from 1 week onwards. Each week blood samples were taken every 12 min for 4 h and plasma assayed for LH. Mean concentration over 4 h, LH pulse frequency and LH pulse amplitude showed no progressive change in 1.5 M sheep. However, in both 0.5 M and 0.5 M + P groups mean LH increased (P < 0.001 and P < 0.01 respectively), pulse frequency decreased (P < 0.01 and P < 0.01) and pulse amplitude increased (P < 0.001 and P < 0.01) over the 10-week period. Anterior pituitary. LH content was greater in 0.5 M (P < 0.01) and 0.5 M + P (P < 0.05) than in 1.5 M sheep. Coronal sections (20 microns) of hypothalamic brain tissue were subjected to in situ hybridisation to determine gene expression for neuropeptide Y (NPY). NPY mRNA was concentrated in the arcuate nucleus and median eminence, with total amounts greater in both 0.5 M (310%, P < 0.001) and 0.5 M + P (333%, P < 0.01) groups than in 1.5 M sheep (100%). These data reveal that chronic low dietary energy intake by long-term castrates, with high or low protein intake, reduces LH pulse frequency but increases the circulating levels of LH by virtue of an increase in pulse amplitude, and concomitantly increases hypothalamic NPY gene expression.

Animals↗
PubMed1996

Regulation of galanin gene expression in the hypothalamic paraventricular nucleus of the obese Zucker rat by manipulation of dietary macronutrients.

Lean and obese male Zucker rats were fed high fat (72% of energy as fat), high carbohydrate (66% of energy as carbohydrate) or intermediate diets for 4 weeks commencing 1 week after weaning. We examined the effects of these diets on growth rates, plasma insulin and corticosterone titres, and hypothalamic gene expression of 3 appetite-related neuropeptides. Messenger RNA levels for neuropeptide Y (NPY), galanin (GAL) and corticotropin-releasing factor (CRF) in critical hypothalamic locations were measured by in situ hybridization in each brain. Obese rats grew more rapidly and had elevated plasma insulin and corticosterone concentrations relative to their lean littermates. The obese phenotype was also associated with elevated NPY gene expression in the arcuate nucleus of the hypothalamus and increased GAL gene expression in the hypothalamic paraventricular nucleus. There was no effect of diet on NPY or CRF gene expression in either lean or obese rats. However, maintenance on the high fat diet had a significant effect on GAL gene expression in obese but not lean rats: high fat diet significantly reduced mRNA levels in the obese rats. This reduction in GAL mRNA was accompanied by attenuation of the hyperinsulinemia that is characteristic of this genetic obesity.

Animals↗
PubMed1996

Melatonin suppresses the induction of AP-1 transcription factor components in the pars tuberalis of the pituitary.

In ovine pars tuberalis cells which express high affinity Mel 1a melatonin receptors, the ability of melatonin to directly stimulate or inhibit AP-1 transcription factor gene expression was studied. Effects of melatonin upon mRNA expression by forskolin, serum and IGF-1 were also investigated. Northern analysis showed melatonin had no direct stimulatory nor inhibitory effect upon transcription or translation. Melatonin was able to significantly inhibit forskolin-stimulated induction of c-fos and jun B mRNA whilst forskolin had no effect upon c-jun or jun D. Induction of c-Fos translation by forskolin was also inhibited by melatonin. Serum induced c-fos and c-jun, but melatonin was unable to affect these changes. Similarly IGF-1 stimulated c-fos and melatonin had no effect upon this induction. From these results it can be concluded that melatonin has no independent effects on expression of the AP-1 genes, rather its primary function is to inhibit cell activities through cyclic AMP-dependent routes of gene activation.

Animals↗
PubMed1996

Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization.

Expression of the leptin receptor gene has been examined in mouse hypothalamus and other brain regions by in situ hybridization. With a probe recognizing all the known splice variants, receptor mRNA was evident in several brain regions (cortex, hippocampus, thalamus), with strong expression in the hypothalamus (arcuate, ventromedial, paraventricular and ventral premammillary nuclei), choroid plexus and leptomeninges. A probe specific to the long splice variant of the leptin receptor (Ob-Rb), containing the putative intracellular signaling domain, again revealed strong expression in the hypothalamus; there was, however, minimal hybridization to choroid plexus and leptomeninges. These results indicate that the hypothalamus is a key site of leptin action, although other brain regions are also targeted.

Alternative Splicing↗
PubMed1996

Hypothalamic NPY and CRF gene expression in the food-deprived Syrian hamster.

Because the Syrian hamster, Mesocricetus auratus, does not increase food intake in response to food deprivation, we investigated whether hypothalamic NPY gene expression in this species was sensitive to this imposed state of negative energy balance. In the rat, food deprivation for 48 h resulted in a 150% increase in total preproNPY gene expression in the arcuate nucleus of the hypothalamus (ARC). NPY gene expression in food-deprived Syrian hamsters did not differ significantly from that of ad lib-fed controls, although there was a trend towards increased mRNA levels in the fasted animals. However, food deprivation for 48 h was associated with a rise in preproCRF mRNA in the paraventricular nucleus of the hypothalamus (PVN) of 80-g, but not 150-g, hamsters. The expected reductions in plasma insulin accompanied food deprivation in the Syrian hamster, but cortisol titre was only elevated in the lower body weight group. NPY gene expression in the Syrian hamster appeared, however, to be sensitive to glucocorticoids; daily administration for 28 days of the synthetic glucocorticoid, dexamethasone, increased ARC NPY mRNA levels by 43%. The response of NPYergic and other hypothalamic neuropeptide systems to food deprivation, and the involvement of neuroendocrine substrates in energy homeostasis, may vary between species.

Animals↗