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Leptin Treatment (leptin + treatment)
Selected AbstractsThe Role of the Vagus Nerve in Mediating the Long-Term Anorectic Effects of LeptinJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2007C. Sachot Leptin, the product of the obese (ob) gene, is mainly known for its regulatory role of energy balance by direct activation of hypothalamic receptors. Recently, its function in the acute control of food intake was additionally attributed to activation of the vagus nerve to regulate meal termination. Whether vagal afferent neurones are involved in longer term effects of leptin on food intake, however, remains undetermined. Using vagotomised (VGX) rats, we sought to clarify the contributions of vagal afferents in mediating the long-lasting effect of leptin on appetite suppression. Intraperitoneal (i.p.) injection of leptin (3.5 mg/kg) attenuated food intake at 4, 6, 8 and 24 h and body weight at 24 h postinjection in SHAM-operated rats; however, this response was not abrogated by vagotomy. In a separate study using immunohistochemistry, we observed leptin-induced Fos expression in the nucleus tractus solitarii, a brain structure where vagal afferent fibres terminate. This signal was not attenuated in VGX animals compared to the SHAM group. Moreover, leptin treatment led to a similar level of nuclear STAT3 translocation, a marker of leptin signalling, in the hypothalami of SHAM and VGX animals. In addition to the effects of leptin, vagotomy surgery itself resulted in a decrease of 24 h food intake. Analyses of brains from saline-treated VGX animals revealed a significant induction of Fos in the nucleus tractus solitarii and changes in agouti-related peptide and pro-opiomelanocortin mRNA expression in the hypothalamus compared to their SHAM counterparts, indicating that the vagotomy surgery itself induced a modification of brain activity in areas involved in regulating appetite. Collectively, our data suggest that vagal afferents do not constitute a major route of mediating the regulatory effect of leptin on food intake over a period of several hours. [source] Altered Expression of SOCS3 in the Hypothalamic Arcuate Nucleus during Seasonal Body Mass Changes in the Field Vole, Microtus agrestisJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2007E. Król We have previously shown that cold-acclimated (8 °C) male field voles (Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD, 16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than animals maintained in SD. By infusing voles with exogenous leptin, we have also demonstrated that SD voles respond to the hormone by reducing body mass and food intake, whereas LD animals increasing body mass are resistant to leptin treatment. In the present study, we investigated whether seasonal changes in body mass could be linked to modulation of the leptin signal by suppressor of cytokine signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up to 11 weeks. LD voles increasing body mass had significantly higher levels of SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated changes in expression of NPY, AgRP, POMC and CART genes. These results suggest that voles that regulate body mass at either the lower (SD) or upper (LD) plateau remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a short-term mechanism that enables animals to move between the stable body mass plateaus. Our data provide evidence that expression of SOCS3 in the ARC is involved in the modulation of the strength of the leptin signal to facilitate seasonal cycles in body mass and adiposity. [source] Leptin Uptake by Serotonergic Neurones of the Dorsal RapheJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2002M. C. Fernández-Galaz Abstract The effects of leptin on food intake, metabolism, sleep patterns and reproduction may be mediated, in part, by the midbrain serotonergic systems. Here, we report on the distribution of neurones that accumulate leptin in the raphe nuclei of male and female rats after intracerebroventricular administration of mouse recombinant leptin labelled with digoxigenin. Direct leptin-targeted cells were present in the periventricular grey, pontine and raphe nuclei. Confocal microscopy revealed that raphe neurones which accumulated leptin were predominantly serotonergic. The temporal pattern of leptin accumulation by raphe neurones showed a marked gender difference: 6 h after leptin administration, all male and female rats showed massive leptin binding in the dorsal raphe, while 30 min after leptin treatment, only 10% of male rats exhibited leptin-labelled cells in contrast to 50% of females. The present observations reveal that leptin can be selectively accumulated by serotonergic neurones in the raphe nuclei and that this mechanism is gender specific. These findings support the idea that the midbrain serotonergic system is an important mediator of the effects of leptin on brain function and may provide an explanation for gender differences in metabolism regulation and its coordination with higher functions of the brain. [source] Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunitsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2007Claire-Dominique Walker Abstract The high circulating levels of leptin in neonatal rodents do not seem to be regulating energy balance at this age, but rather may play an important role for brain development. We tested the hypothesis that high neonatal leptin levels modify hippocampal function and production of synaptic proteins with possible long-term consequences on long-term potentiation (LTP) in adulthood. We first showed that in postnatal day (PND) 10 neonates, acute leptin treatment functionally activated leptin receptors (ObR) in the CA1 and DG regions of the hippocampus through the induction of phosphoERK1/2, but not phosphoSTAT3 protein although both phospho-proteins were induced in the arcuate nucleus. We next examined whether chronic leptin administration (3 mg/kg BW, intraperitoneally) during the first 2 weeks of life (postnatal day, PND 2,14) produces a functional signal in the hippocampus that alters the expression of NMDA receptor subunits (NR1, NR2A, NR2B), synaptic proteins and LTP in the short and long-term. In PND 10 as in adults (PND 70) rats, chronic leptin treatment increased NR1 expression in the hippocampus while reducing NR2B protein levels. Elevated hippocampal concentrations of synapsin2A and synaptophysin were detected during leptin treatment on PND 10 suggesting increased neurotransmitter release. In adults, only SNAP-25 expression was increased after neonatal leptin treatment. LTP was reduced dramatically by leptin treatment in preweaning rats although the changes did not persist until adulthood. Elevated exposure to leptin during a critical period of neonatal hippocampal development might serve to enhance NMDA-dependent functions other than LTP and have important effects on synaptogenesis and neurotransmitter release. © 2007 Wiley-Liss, Inc. [source] Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashionMOLECULAR CARCINOGENESIS, Issue 1 2008Jenifer I. Fenton Abstract The imbalance in systemic mediators of inflammation, such as leptin, is thought to be involved in obesity-associated cancers. In addition, systemic endocrine signals can influence the local autocrine/paracrine factors produced within this microenvironment to influence epithelial cell fate. We previously demonstrated that leptin preferentially promotes the survival and proliferation of colon epithelial cells possessing an Apc mutation (IMCE) but not model normal cells (YAMC). Therefore, the purpose of this study was to identify leptin-induced functional gene family changes which characterize the response of colon epithelial cells possessing an Apc mutation but not normal cells. Consistent with our knowledge of colon carcinogenesis, genes regulating the Wnt/,-catenin-mediated pathway including Mdm2, Pik3r1, and Rb1 were upregulated by leptin. Importantly, leptin induced IGF-mediated pathway gene expression changes and their protein products in IMCE cells. In the IMCE cells IGFBP-6, IGF-1, and Crim1 expression was upregulated, while IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and Nov expression was downregulated by leptin treatment. These data establish a biologically plausible mechanistic link between the elevated levels of growth factors and the increased risk of colon cancer associated with obesity. © 2007 Wiley-Liss, Inc. [source] | ||||||||||