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

Stress can cause disturbance of homeostasis to result in illness. Stress can also induce various gene expression in different neuronal systems. For example, nutritional stress induced by acute food deprivation upregulates corticotropin-releasing factor (CRF) mRNA, whereas osmotic stress increases vasopressin (VP) mRNA. However, it is unknown if nutritional stress induced by chronic food deprivation has synergistic effects on CRF and VP mRNAs. We have used in situ hybridization in conjunction with quantitative autoradiography to demonstrate that nutritional stress induced by a 4-day food deprivation results in a body-weight loss with a significant decrease of CRF mRNAs, but not VP mRNAs in the paraventricular hypothalamic nucleus (PVN) of Sprague-Dawley rats. The present study has thus indicated that a chronic nutritional stress does not have synergistic effects on CRF and VP mRNAs. The decrease of CRF mRNAs is obviously related to the body-weight loss induced by food deprivation. This study thus supports a notion that the CRF, but not VP, neurons in the PVN play an important role in their neuroadaptation associated with body weight loss. Thus, it is conceivable that downregulated CRF neurons in the hypothalamus could be involved in pathogenesis of human eating disorder with severe weight loss, whereas upregulated CRF neurons could be associated with an opposite form of the eating disorder that causes obesity.
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PMID:Downregulation of corticotropin-releasing factor mRNA, but not vasopressin mRNA, in the paraventricular hypothalamic nucleus of rats following nutritional stress. 925 Jun 25

In a brief review of advances in endocrinology in the last two years the author discusses above all the vain expectations of a drug against obesity-the adipose tissue hormone leptin. Its elevated blood level in human obesity indicates that its secretion depends on the mass of adipose tissue and it is not certain whether leptin reduces the food intake in humans. Perhaps resistance to leptin is involved. New receptor diseases were revealed: mutation of LH receptors leads in both sexes to hypogonadism. Mutation of the calcium receptor in parathyroid cells leads to familial hypocalciuric hypercalcaemia or autosomal dominant hypocalcaemia. The complex regulation of the tonus of the vascular wall by endothelins is still the object of interest. Aquaporin is a renal protein which mediates the action of vasopressin. In the sphere of stress evidence is emerging on the participation of CRH in brain activity and the possibility to influence autoimmune inflammations and perhaps even AIDS by interference with the CRH-proopiomelanocortin-ACTH-cortisol system.
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PMID:[Endocrinology 1995-1996]. 926 67

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

Albright hereditary osteodystrophy (AHO), an autosomal dominant disorder characterized by short stature, obesity, and skeletal defects, is associated with heterozygous inactivating mutations of GNAS1, the gene encoding the heterotrimeric G protein alpha-subunit (Gsalpha) that couples multiple receptors to the stimulation of adenylyl cyclase. It has remained unclear why only some AHO patients present with multihormone resistance and why AHO patients demonstrate resistance to some hormones [e.g., parathyroid hormone (PTH)] but not to others (e.g., vasopressin), even though all activate adenylyl cyclase. We generated mice with a null allele of the mouse homolog Gnas. Homozygous Gs deficiency is embryonically lethal. Heterozygotes with maternal (m-/+) and paternal (+/p-) inheritance of the Gnas null allele have distinct phenotypes, suggesting that Gnas is an imprinted gene. PTH resistance is present in m-/+, but not +/p-, mice. Gsalpha expression in the renal cortex (the site of PTH action) is markedly reduced in m-/+ but not in +/p- mice, demonstrating that the Gnas paternal allele is imprinted in this tissue. Gnas is also imprinted in brown and white adipose tissue. The maximal physiological response to vasopressin (urinary concentrating ability) is normal in both m-/+ and +/p- mice and Gnas is not imprinted in the renal inner medulla (the site of vasopressin action). Tissue-specific imprinting of Gnas is likely the mechanism for variable and tissue-specific hormone resistance in these mice and a similar mechanism might explain the variable phenotype in AHO.
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PMID:Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene. 967 44

Obesity constitutes an important problem of public health in developed countries because of its high prevalence (affecting nearly one third of the population) and the reduction of life expectancy in this population. Every day new physiopathologic implications are discovered concerning obesity and other cardiovascular risk factors such as diabetes, hypertension and dyslipemia. We present the mechanisms that explain the physiopathology of obesity from the point of view of hemodynamic modifications, neurohormonal alterations (sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, endothelin), and alterations in the glucidic metabolism (insulin-resistance and hyperinsulinism), the lipidic metabolism and the endothelium. The treatment of obese hypertensive patients is based on two principles: the correction of overweight and the treatment of hypertension, bearing ind mind the peculiarities in these patients.
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PMID:[Obesity and arterial hypertension]. 988 64

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

Differentiating Cushing's disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 microg DDAVP. Sixty-one of these subjects also underwent a control study with saline. DDAVP induced marked ACTH and cortisol rises in CD (P < 0.005 vs. saline, for both ACTH and cortisol) but not in PC. A significant ACTH elevation occurred upon DDAVP administration also in normal and obese subjects, but it was much smaller than that observed in patients with CD (P < 0.0001). A peak absolute ACTH increase (> or =6 pmol/L), after DDAVP, allowed us to recognize 66 of 76 patients with CD and 88 of 97 subjects of the other groups. The same criterion correctly identified 18 of 20 patients with mild CD (24-h urinary free cortisol < or = 690 nmol/day) and 29 of 30 PC, resulting in a diagnostic accuracy of 94%, which was definitely higher than that displayed by urinary free cortisol, overnight 1-mg dexamethasone suppression test, and midnight plasma cortisol. In conclusion, the DDAVP test seems to be a useful adjunctive tool for the evaluation of hypercortisolemic patients chiefly because of its ability to differentiate mild CD from PC states.
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PMID:The desmopressin test in the differential diagnosis between Cushing's disease and pseudo-Cushing states. 1106 3

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

This review discusses the possible interrelationships between adrenal steroid hormones and the metabolic syndrome. Abnormal regulation of the hypothalamic-pituitary-adrenal axis has been proposed. Studies in the United Kingdom associated the metabolic syndrome with low birth weight and hyperactivity of the entire axis. In Italy, increased pituitary responsiveness to stimulation with vasopressin and corticotrophin-releasing hormone was demonstrated in women with central obesity. Swedish researchers have reported that increased stress responses of the axis correlated with a less variable but decreased cortisol level. An allele of the glucocorticoid receptor was also associated with various components of the metabolic syndrome. Evidence also suggests that central obesity is associated with an increased peripheral conversion of cortisol to cortisone and subsequent feedback stimulation of the axis. On the other hand, central fat may have an increased local metabolism in the direction of cortisol. Roles for dehydroepiandrosterone and aldosterone in the syndrome have also been proposed.
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PMID:The adrenal and the metabolic syndrome. 1127 91


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