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

Plasma leptin levels are elevated in most obese individuals, and obesity is accompanied by a high incidence of cardiovascular disease. Therefore, leptin could be involved in the pathogenesis of cardiovascular disease. In the present study, the role of leptin was explored in the regulation of platelet function. The expression of the long form of the leptin receptor was detected in human platelets. At 50 ng/ml, human leptin induced phosphorylation of several proteins of platelets at the tyrosine residue. Neither leptin at concentrations < or = 100 ng/ml nor ADP at concentrations > or = 1 micromol/l affected platelet aggregation. However, after pretreatment with 100 ng/ml leptin for 5 min, 1 micromol/l ADP caused aggregation. Thus, leptin and ADP acted synergistically. At a concentration of 2 micromol/l, ADP induced platelet aggregation, which was markedly enhanced by 30-100 ng/ml leptin in a concentration-dependent manner. This concentration range corresponds to that of plasma leptin levels in obese individuals. At the lower concentrations (< 10 ng/ml) that are observed in normal individuals, leptin had no effect on platelet aggregation. In conclusion, leptin at high concentrations has the novel function of promoting platelet aggregation, which may be a key coupling factor between obesity and the cardiovascular disease associated with syndrome X and diabetes.
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PMID:Leptin promotes aggregation of human platelets via the long form of its receptor. 1033 26

This study examines the effects of the leptin receptor mutation in obese Zucker rats on entrainment of food-anticipatory rhythms to daily feeding schedules. Leptin is secreted by adipocytes in proportion to fat content, exhibits a daily rhythm in plasma that is synchronized to feeding time, and inhibits activity of arcuate neuropeptide Y neurons that stimulate feeding behavior and regulate metabolism. Activity within this neuropeptide Y system is enhanced by food deprivation and attenuated by overfeeding and diet-induced obesity. Diet-induced obesity, in turn, attenuates food-anticipatory rhythms. If the effects of obesity on food-entrained rhythms are mediated by leptin inhibition of neuropeptide Y neurons, then these rhythms may be enhanced in leptin-insensitive Zucker obese rats. Alternatively, if daily rhythms of leptin mediate the generation or entrainment of these rhythms, Zucker rats may fail to anticipate daily feedings. Zucker obese and lean rats received food for 3 h/day during the midlight period. Both groups exhibited significant food-anticipatory activity that persisted during three cycles of food deprivation, but this rhythm was significantly more robust in obese rats, when expressed as anticipation and persistence ratios, and as peak values. Anticipatory rhythms did not persist in either group when food was provided ad lib. These results indicate that central actions of leptin may mediate the inhibitory effects of obesity on the expression of food-anticipatory rhythms in rats, but do not mediate the inhibitory effects of ad lib food access, and do not serve as necessary internal entrainment cues or clock components for the food-entrainable circadian system.
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PMID:Enhanced food-anticipatory circadian rhythms in the genetically obese Zucker rat. 1033 62

It is currently well established that the nervous, endocrine and immune systems inter-communicate using biologically active soluble factors, synthesised and produced by these three systems themselves (e.g. immunomodulator effect of hormones, effect of substances secreted by immune cells on endocrine function.). In addition, these systems jointly express receptors for hormones, peptides, growth factors and cytokines. Immuno-neuroendocrine interactions therefore underlie physiological processes and their deregulation can result in various pathological states. By entering into complex relationships with the specialized and differentiated cells of these three systems viruses can alter inter-cellular communication and result in the appearance of pathological processes directly linked to these disturbances. In order to understand the role of viruses in the genesis of neuroimmunoendocrine pathologies, we have developed a cerebral infection model using canine distemper virus (CDV). In infected mice, this paramyxovirus, closely related to the human measles virus, induces early neurological pathologies (encephalitis) which are associated with active viral replication. Mice surviving the acute phase of infection exhibit motor deficits (paralysis and turning behaviour) or obesity during the viral persistence phase, despite the fact that the virus is no longer detectable. The obesity is characterised by hyperinsulinaemia, hyperleptinaemia and hyperplasia of the adipocytes, associated with decreased expression of the OB-Rb hypothalamic leptin receptor and modulated expression of hypothalamic monoamines and neuropeptides. These results support the viral "hit and run" theory, since the initial viral impact in the hypothalamus may be the origin of the changes in later immunoneuroendocrine communication. Thus, certain human neurodegenerative or neuroendocrine diseases may have a previous viral infection aetiology without it being possible to clearly identify the agent responsible.
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PMID:[Viruses and the neuroendocrine system: model of murine obesity induced by cerebral infection by canine distemper virus]. 1037 79

Genetic studies in inbred obese mice have revealed the ob gene, its product leptin and the leptin receptor as important factors in the regulation of both appetite and energy expenditure. Treatment with recombinant leptin has resulted in a marked weight reduction in obese animals with ob gene mutations as well as in normal mice. Also mutations in the Ob receptor gene result in marked obesity in rodents. These data have given hope of new treatment options in obesity. Further support of leptin being involved in regulation of obesity in man comes from the observation that inactivating mutations in the human ob gene lead to profound early onset obesity. However, the role of leptin and its feedback system in man is still only partly revealed. This review focuses on our present knowledge and hypotheses about the leptin pathway in humans and its potential importance in the clinic of obesity.
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PMID:Leptin and its potential role in human obesity. 1039 94

There are reports on some patients with clearly manifested specific features of genotype and phenotype similar to those of ob/ob and db/db mice. Three patients from Turkey were described who had a homozygous mutation in the gene of leptin identical to the mutation in C57BL6J ob/ob mice. This mutation is a C --> T substitution in codon 105 of the amino acid sequence of leptin. In mice this mutation generates a stop-codon; in humans it substitutes Arg-105 with Trp. The mutant human leptin cannot be secreted by the cells and thus has no effect on the hypothalamus. Patients with a homozygous mutation of the leptin receptor resulting in the G --> T substitution in the splice donor site of exon 16 were studied in a family of Kabilian origin. Exon 16 was not included in the mature mRNA molecule, and a truncated leptin receptor was synthesized which lacked the transmembrane and intracellular domains; this receptor was unable to transduce the hormonal signal. Both groups of patients suffered from obesity, delayed linear growth, infertility, increased blood insulin level, and other disorders. Leptin influences lipid metabolism by stimulating the expression of the proopiomelanocortin (POMC) gene in melanocortinergic neurons of the hypothalamus. POMC is the precursor of alpha-melanocyte-stimulating hormone (alpha-MSH), which binds to the melanocortin receptor MC4-R in the brain, decreases appetite, and activates lipid metabolism. Patients with mutations in MC4-R suffered only from obesity, but their growth and puberty were not affected. Thus, leptin apparently stimulates growth and puberty not through its binding to the receptors on melanocortinergic neurons, but through its binding to receptors on other hypothalamic neurons; this effect of leptin is not affected by mutations in the MC4-R gene.
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PMID:Adipose tissue as an endocrine organ regulating growth, puberty, and other physiological functions. 1039 72

A major paradigm in the field of obesity research is the existence of an adipose tissue-brain endocrine axis for the regulation of body weight. Leptin, the peptide mediator of this axis, is secreted by adipose cells. It lowers food intake and body weight by acting in the hypothalamus, a region expressing an abundance of leptin receptors and a variety of neuropeptides that influence food intake and energy balance. Among the most promising candidates for leptin-sensitive cells in the hypothalamus are arcuate nucleus neurons that co-express the anabolic neuropeptides, neuropeptide Y (NPY) and agouti-related peptide (AGRP), and those that express proopiomelanocortin (POMC), the precursor of the catabolic peptide, alphaMSH. These cell types contain mRNA encoding leptin receptors and show changes in neuropeptide gene expression in response to changes in food intake and circulating leptin levels. Decreased leptin signaling in the arcuate nucleus is hypothesized to increase the expression of NPY and AGRP. Levels of leptin receptor mRNA and leptin binding are increased in the arcuate nucleus during fasting, principally in NPY/AGRP neurons. These findings suggest that changes in leptin receptor expression in the arcuate nucleus are inversely associated with changes in leptin signaling, and that the arcuate nucleus is an important target of leptin action in the brain.
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PMID:Leptin sensitive neurons in the hypothalamus. 1042 33

Leptin, a protein encoded by the ob gene, is an adipose tissue-derived signaling factor involved in body weight homeostasis. The hypothalamus is a major site of central action for leptin. However, mounting evidence indicates expression of leptin receptor mRNA in various peripheral organs including the adrenal medulla. Therefore, we investigated the effects of leptin on catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. We initially confirmed the expression of leptin receptor (Ob-Rb) mRNA in cultured porcine adrenal medullary cells. Murine recombinant leptin (>==50 nM) strongly induced the release of both epinephrine (E) and norepinephrine (NE) from chromaffin cells. Removal of external Ca(2+) significantly suppressed these effects. Also, leptin (>==1 nM) enhanced nicotine-induced increases in E- and NE. Leptin (1, 10, 100 nM) significantly increased tyrosine hydroxylase (TH) (a rate-limiting enzyme in the biosynthesis of catecholamine) mRNA levels in a concentration-dependent manner. Furthermore, leptin (1, 10, 100 nM) significantly induced increases in cAMP levels, suggesting that the stimulatory effects on TH mRNA are mediated, at least in part, by the cAMP/protein kinase A pathway. These results indicate that leptin directly stimulates catecholamine release and synthesis, which in turn may potentiate the anti-obesity effects of leptin.
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PMID:Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. 1042 1

We reported previously an increase in leptin receptor (OBR) gene expression in the anterior pituitary of human GH-releasing hormone (hGHRH) transgenic mice. The primary goal of this study was to investigate the possible mechanisms regulating OBR expression in these mice. Compared with normal sibling controls, hGHRH transgenic mice had significantly greater amounts of abdominal fat, higher levels of leptin messenger RNA (mRNA), and a 2-fold increase in plasma leptin concentrations. Despite normal plasma glucose levels, hGHRH transgenic mice had 4.5-fold elevated levels of plasma insulin. Using a ribonuclease protection assay, we measured the mRNA levels of the OBR long form (OBR(L)) in the anterior pituitary and hypothalamus after 48 h of fasting. In the anterior pituitary, food deprivation induced dramatic increases in OBR(L) mRNA levels in both normal and transgenic mice. In contrast, in the hypothalamus, fasting resulted in a significant decrease in OBR(L) gene expression in normal mice, and no changes were detected in hGHRH transgenic mice. Using dual in situ hybridization, OBR(L) mRNA was detected in somatotrophs. Moreover, the number of OBR(L)-positive pituitary cells as well as the percentage of OBR(L)-positive cells that express GH mRNA were increased in transgenic mice. In conclusion, 1) the modest obesity in hGHRH transgenic mice is associated with increases in leptin synthesis and secretion as well as insulin secretion; 2) GH and/or GHRH as well as leptin and insulin may differentially contribute to the changes in OBR(L) gene expression in the anterior pituitary and the hypothalamus; 3) the response of OBR(L) gene expression in the hypothalamus to fasting is absent in the modestly obese hGHRH transgenic mice; and 4) somatotrophs are target cells for leptin, and the increase in OBR(L) gene expression in the pituitary of hGHRH transgenic mice is due at least in part to the increase in the number of cells expressing OBR(L).
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PMID:The human growth hormone-releasing hormone transgenic mouse as a model of modest obesity: differential changes in leptin receptor (OBR) gene expression in the anterior pituitary and hypothalamus after fasting and OBR localization in somatotrophs. 1043 18

Viruses can induce progressive neurologic disorders associated with diverse pathological manifestations, and therefore, viral infection of the brain can impair differentiated neural functions, depending on the initial viral tropism. We have previously reported that canine distemper virus (CDV) targets certain mouse brain structures, including the hypothalamus, early and selectively. Infected mice exhibit acute encephalitis, with late disease, characterized by motor impairment or obesity syndrome, appearing in some of the surviving mice several months after the initial viral replication. In the present study, we show viral persistence in the hypothalami of obese mice, as demonstrated by low, but still significant, levels of CDV nucleoprotein transcripts, associated with a dramatic decrease in F gene mRNAs. Given the pivotal role of the hypothalamus in obesity (eating behavior, energy consumption, and neuroendocrine function) and that of leptin, the adipose tissue-derived satiety factor acting through hypothalamic receptors, we analyzed the leptin networks in both obese and nonobese mice. The discrepancy found between the chronic and dramatic increase in blood leptin levels and the occurrence of obesity may be due to leptin resistance in the brain. In fact, expression of the long leptin receptor isoform, representing the functional leptin receptor, was specifically downregulated in the hypothalami of obese mice, explaining their inability to generate an adequate response to leptin in the brain. Intriguingly, during the acute phase of infection, its expression was increased in CDV-targeted structures in all infected mice and remained high in obese mice in all CDV-targeted structures, except for the hypothalamus. The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV-induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological, virus-induced abnormalities.
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PMID:Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus. 1043 20

The recent discovery of leptin as a major controller of appetite has led to a detailed analysis of its specific actions in this process as well as any potential role in the etiology of obesity. It has also emerged that leptin has a wider spectrum of biological activities and has been strongly implicated in fertility and reproduction. The structural similarity between leptin and its receptor and cytokine-receptor systems that control hemopoiesis has also prompted investigation of the potential for this hormone to influence blood cell formation. Recent studies have shown that the leptin receptor is expressed on a diverse range of hemopoietic cells. Leptin itself appears to enhance proliferation of hemopoietic cells in vitro, particularly in combination with other cytokines and may augment some mature hemopoietic cell functions. Although only relatively minor hemopoietic deficiencies have been reported in mice lacking leptin or its receptor, these emerging studies suggest that further analysis of leptin actions in hemopoiesis may be warranted.
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PMID:A role for leptin in hemopoieses? 1046 69


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