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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal experiments have shown that the parvocellular oxytocin (OXT) neurons of the hypothalamic paraventricular nucleus (PVN) inhibit food intake. In the present study, the PVN and its OXT neurons have been investigated in an extreme human eating disorder, i.e. the Prader-Willi syndrome (PWS). PWS patients are characterized by gross obesity, insatiable hunger, hypotonia, hypogonadism, and mental retardation. The PVN of 5 PWS patients (2 males and 3 females), varying in age between 22-64 yr, and 27 controls (14 males and 13 females) without any primary neurological or psychiatric diseases was morphometrically investigated after conventional staining with thionine and immunocytochemical staining for OXT and vasopressin (AVP). The thionine-stained volume of the PVN was 28% smaller in PWS patients (P = 0.028), and the total cell number was 38% lower (P = 0.009). The immunoreactivity for OXT and AVP was decreased in PWS patients, although the variability within the groups was high. A strong and highly significant decrease (42%; P = 0.016) was found in the number of OXT-expressing neurons of the PWS patients. The volume of the PVN-containing OXT-expressing neurons decreased by 54% (P = 0.028) in PWS. The number of AVP-expressing neurons in the PVN did not change significantly. The OXT neurons of the PVN seem to be good candidates for playing a physiological role in ingestive behavior as "satiety neurons" in the human hypothalamus.
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PMID:Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. 785 23

Most cases of postpartum haemorrhage are caused by uterine atony, maternal soft-tissue trauma, retained placenta or its parts, and obstetric coagulopathy. The factors most significantly associated with haemorrhage include advanced maternal age, prolonged labour, pre-eclampsia, obesity of mother, multiple pregnancy, a birth weight of more than 4000g, and previous postpartum haemorrhage. It seems that multiparity itself is only a weakly associated factor. The prophylactic use of oxytocic drugs (oxytocin or its combination with ergometrine at the third stage of labour is always recommended for decreasing the bleeding. Prostaglandins should be used as a second line treatment if uterine atony cannot be abolished by uterine massage and oxytocin infusion. In the surgical management, the role of hypogastric artery ligation is decreasing. The stepwise uterine devascularization may be a reasonable method in the most severe uncontrollable postpartum bleeding. The uterine tamponade with gauze or specific tubes may also be a useful alternative in some cases. Selective arterial embolization is a promising new method that seems to have success in controlling the heavy postpartum bleeding unresponsive to more usual measures. However, the value of this method should be evaluated in bigger series.
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PMID:Postpartum haemorrhage. 862 78

Dysfunction of various hypothalamic systems may be the basis of a number of symptoms in Prader-Willi syndrome. The often abnormal position of the baby in the uterus at the onset of labour, the high percentage of infants with asphyxia and the high proportion of children born prematurely or post-maturely may all be related to abnormal fetal hypothalamic systems, as the fetal hypothalamus plays a crucial role in labour. Abnormal luteinizing hormone-releasing hormone neurones are thought to be responsible for the decreased levels of sex hormones, resulting in non-descended testes, undersized sex organs and insufficient growth during puberty. A lack of growth hormone-releasing hormone may also contribute to the short stature of patients with Prader-Willi syndrome. In addition, the aberrant control of body temperature and daytime hypersomnolence may result from hypothalamic disturbances. The number of oxytocin neurones--the putative satiety neurones--in the hypothalamic paraventricular nucleus is markedly decreased in Prader-Willi syndrome. This is presumed to be the basis of the insatiable hunger and obesity of patients with the syndrome.
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PMID:Prader-Willi syndrome and the hypothalamus. 940 39

Leptin, a product of the obese (ob) gene, is secreted by adipocytes and appears to act as a hormone to regulate food intake, metabolism and body weight. Subcutaneous administration of leptin causes reductions in food intake and body and fat-depot weights in both lean and genetically obese (ob/ob) mice, and leptin infusion into the lateral cerebral ventricles decreases feeding with short latency, suggesting a central site of action. A gene defect in the Zucker obese rat causes an amino acid substitution in the leptin receptor and reduced leptin binding at the cell surface. An antiserum to a portion of the mouse leptin receptor (AA 877-894) located within the intracellular domain was used to label Zucker lean (Fa/?) and obese (fa/fa) rat brain sections. At optimal dilution (1:8000), only cells in the basal forebrain, preoptic area, hypothalamus and brainstem were moderately or intensely labeled. The most intensely-labeled nuclei, the anterior commissural, magnocellular paraventricular, supraoptic, circularis in the anterior hypothalamus and fornical in the lateral hypothalamus contain large neurons that synthesize and secrete vasopressin or oxytocin and their respective neurophysins. Diminished leptin transport into the central nervous system or defective signal transduction in Zucker obese rats may sufficiently compromise leptin regulation of the HPA axis, NPY-immunoreactive neurons or other hypothalamic elements to cause obesity.
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PMID:Localization of leptin receptor immunoreactivity in the lean and obese Zucker rat brain. 952 52

1. Studies of the regulation of neurosecretory cell gene expression suffer from the lack of suitable cell lines. Two approaches have been used to overcome this deficit: transfection of neuropeptide genes into heterologous cell lines and generation of transgenic animals. 2. Studies with heterologous cell lines have revealed the potential involvement of nuclear hormone receptors, POU proteins, and fos/jun/ATF family members in the regulation of the vasopressin and oxytocin genes. Although limited in their scope, these studies have contributed greatly to the dissection of basic properties of elements in the vasopressin and oxytocin gene promoters. 3. Transgenic mice, and more recently rats, have been used to elucidate genomic regions governing cell specificity and physiological regulation of neurosecretory gene expression. The genes encoding the neuropeptides vasopressin and oxytocin have been used in many transgenic studies, due to the well-defined expression patterns and physiology of the endogenous neuropeptides. Cell-specific and physiologically regulated expression of these transgenes has been achieved, demonstrating the action of putative repressor elements and regulation of the expression of one gene by sequences present in the other gene. 4. Appropriate expression and translation of transgenes have resulted in the production of several useful systems. Expression of oncogene sequences in gonadotropin-releasing hormone neurons has allowed the development of cell lines from the resulting tumors, overproduction of corticotropin-releasing factor has produced animal models of anxiety and obesity, and directed ectopic expression of growth hormone has generated a potentially useful rat model of dwarfism. These and other animal models of human disease will provide important avenues for the development of therapeutic strategies.
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PMID:Transgenic and transcriptional studies on neurosecretory cell gene expression. 953 88

Galanin and galanin receptors are widely distributed within the central nervous system, but historically much research has been focused on hypothalamic galanin systems including those in the preoptic area, paraventricular nucleus (PVN), supraoptic nucleus (SON), and median eminence. In early studies, galanin mRNA, immunoreactivity, and binding sites were detected in neurons of the SON and both the magnocellular and parvocellular regions of the PVN, all of which also contain vasopressin, oxytocin, and several other peptides. This article briefly reviews some important recent studies of the electrophysiologic effects of galanin on magno-cellular neurons in vitro; regulation of galanin expression by the physiologic stimulus of lactation; the role of parvocellular galanin systems in energy balance, body weight, and obesity; and the regional and cellular localization of galanin and galanin receptor mRNAs in the PVN/SON. In relation to the latter issue, two distinct galanin receptor subtypes, GalR1 and GalR2, have now been cloned and characterized. In situ hybridization histochemical studies of rat brain by several groups have consistently demonstrated GalR1 mRNA in the SON and PVN, in the magnocellular and parvocellular regions. By contrast, our recent experiments using [35S]-labeled oligonucleotide probes detected GalR2 mRNA enriched in the parvocellular, not the magnocellular regions of the PVN, and the transcripts were not detected in the SON, whereas studies by other using a digoxigenin-labeled RNA probe have detected GalR2 mRNA in the SON (and PVN). Nonetheless, given the known effects of hyperosmotic stimuli, changes in metabolic status, and various hormones on galanin synthesis and release and the ability of galanin to regulate the electrical and secretory activity of magnocellular neurons, it will be of interest to determine any possible (differential) regulation of galanin receptor subtype expression and the pre- and postsynaptic roles of GalR1 and GalR2 receptors in magnocellular and parvocellular neurons.
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PMID:Galanin-galanin receptor systems in the hypothalamic paraventricular and supraoptic nuclei. Some recent findings and future challenges. 992 75

Diabetes mellitus is not a diagnostic criterion for Prader-Willi syndrome (PWS), but it is often found in PWS patients. The etiology for diabetes mellitus in PWS may be related to the morbid obesity and consequent insulin resistance, because a decrease of oxytocin neurons and leptin resistance in PWS may cause hyperphagia, inducing obesity. However, treatment with growth hormone (GH) is beneficial for the majority of GH-deficient PWS children, because relative decreased fat mass and increased fat-free mass could prevent obesity and concomitant insulin resistance. Hypogonadism is thought to be due to hypogonadotrophic hypogonadism in a majority of PWS patients. Hypergonadotrophic hypogonadism secondary to cryptorchidism and its treatment is shown in other cases. Low luteinizing hormone and high follicle-stimulating hormone levels in PWS cases in young men with idiopathic oligospermia or in the early stages of puberty is less frequently reported.
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PMID:Prader-Willi syndrome, diabetes mellitus and hypogonadism. 1066 37

Objective: To establish the relationship of measured intraoperative blood loss to gestational age at pregnancy termination, and to determine which factors, if any, affect the risk of bleeding.Methods: A single-operator series of 363 consecutive women undergoing pregnancy termination between 5 and 24 weeks gestational age, as dated by ultrasound, was prospectively evaluated. All pregnancies under 13 weeks gestation were terminated by mechanical dilation and suction curettage without preoperative cervical ripening. All pregnancies between 13 and 24 weeks gestation were terminated by preoperative osmotic cervical dilation with laminaria tents and subsequent uterine evacuation by a combination of suction curettage, sharp curettage, and Bierer forceps extraction. All patients over 12 weeks gestation received a postoperative oxytocin infusion. Whenever possible, amniotic fluid and blood were collected and measured separately. Patients were excluded from the data analysis for pregnancy demise, PPROM, Potter's syndrome, or inability to separate blood establish their relationship. After adjustment for gestational age, the results were analyzed to determine if blood loss was related to maternal age, smoking history, body habitus, or operative indication.Results: A curvilinear relationship between blood loss and gestational age was observed. Mean blood loss at 24 weeks exceeded 800 mL. After adjustment for gestational age, no factors significantly affected blood loss at dilation and aspiration of first trimester pregnancies. In those patients undergoing dilation and evacuation in the second trimester, both simple and stepwise regression analyses showed obesity (BMI >/=32.3) to be significantly associated with increased blood loss (P <.05). Neither age, parity, previous cesarean section, nor smoking history were significantly associated with increased blood loss at dilation and evacuation.Conclusions: With advancing gestational age, intraoperative blood loss increases in curvilinear fashion. Termination providers should be advised that, although blood loss is unaffected by many factors, obese patients are at risk for increased bleeding at dilation and evacuation of pregnancies beyond 12 weeks gestation.
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PMID:Intraoperative blood loss and gestational age at pregnancy termination. 1083 89

To establish whether the regulatory mechanism of leptin secretion is sensitive to oxytocin (OT), seven healthy nonobese men were tested with dexamethasone (dex; 4 mg, iv, at 0730 h) in feeding (2000 Cal given at 3 meals over 7 h) conditions either in the absence (iv normal saline infusion) or in the presence of a constant iv infusion of OT (1, 2, or 4 mIU/min from 0730 h for 10 h). In six additional subjects under similar experimental conditions, normal saline or OT (1, 2, or 4 mIU/min from 0730 h for 10 h) were infused iv without the previous treatment with dexamethasone. Serum leptin concentrations were measured in samples taken at 60-min intervals during infusion. Leptin levels remained constant during the infusion of normal saline or OT (1, 2, or 4 mIU/min) alone. In contrast, serum leptin concentrations rose significantly from the baseline after dex administration. The leptin response to dex was not modified by the concomitant infusion of 1 mIU/min OT, whereas it was completely abolished by the administration of 2 or 4 mIU/min OT. These findings led us to evaluate the secretory pattern of leptin in 12 obese patients in similar experimental conditions. In all patients basal leptin levels were significantly higher than those in normal weight subjects. In 6 obese subjects, the infusion of OT alone (1, 2, or 4 mIU/min) was unable to change serum leptin levels. In the remaining 6 obese subjects, dex administration significantly increased serum leptin levels; however, the leptin response to dex was not modified by the concomitant infusion of 1, 2, or 4 mIU/min OT. These data show inhibition by elevated circulating OT levels of glucocorticoid-induced, but not basal, leptin secretion in normal weight subjects, suggesting a possible role for OT in the regulatory control of leptin. Furthermore, the results obtained in obese subjects indicate that this regulation is disrupted in obesity.
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PMID:Effect of systemic oxytocin administration on dexamethasone-induced leptin secretion in normal and obese men. 1106 23

Energy dissipating mechanisms and their regulatory components represent key elements of metabolism and may offer novel targets in the treatment of metabolic disorders, such as obesity and diabetes. Recent studies have shown that a mitochondrial uncoupling protein (UCP2), which uncouples mitochondrial oxidation from phosphorylation, is expressed in the rodent brain by neurons that are known to regulate autonomic, metabolic, and endocrine processes. To help establish the relevance of these rodent data to primate physiology, we now examined UCP2 messenger RNA and peptide expressions in the brain and pituitary gland of nonhuman primates. In situ hybridization histochemistry showed that UCP2 messenger RNA is expressed in the paraventricular, supraoptic, suprachiasmatic, and arcuate nuclei of the primate hypothalamus and also in the anterior lobe of the pituitary gland. Immunocytochemistry revealed abundant UCP2 expression in cell bodies and axonal processes in the aforementioned nuclei as well as in other hypothalamic and brain stem regions and all parts of the pituitary gland. In the hypothalamus, UCP2 was coexpressed with neuropeptide Y, CRH, oxytocin, and vasopressin. In the pituitary, vasopressin and oxytocin-producing axonal processes in the posterior lobe and POMC cells in the intermediate and anterior lobes expressed UCP2. On the other hand, none of the GH-producing cells of the anterior pituitary was found to produce UCP2. The abundance and distribution pattern of UCP2 in the primate brain and pituitary suggest that this protein is evolutionary conserved and may relate to central autonomic, endocrine and metabolic regulation.
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PMID:Mitochondrial uncoupling protein 2 (UCP2) in the nonhuman primate brain and pituitary. 1108 57


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