产品经理设计工具:翻译(有分吆,翻译的好还加分呢??!!我有的是分)

Evidence that MCH synthesis is elevated by both energy restriction and leptin deficiency79,andthatMCH-knockoutmicehavereducedfoodintake andareexcessivelylean80,isconsistentwiththismodel.Thediscovery of the MCH receptor as a G-protein-coupled receptor (previously knownasSLC-1)81,82alsosupportsthehypothesisofMCHasanorexigenicfactor.LikeNPYreceptors,theMCHreceptoriscoupledtothe Gi subunit of the plasma membrane G-protein assembly. By activating Gi, binding of MCH to its receptor inhibits formation of cyclic

AMP and consequently reduces signalling by protein kinase A (PKA)81,82. This effect is opposite to that mediated by activation of receptors that exert anorexic effects, such as MC4 or CRH receptors, which are coupled to Gs and consequently increase cAMP and PKA signalling. Two additional peptides are expressed exclusively in the LHA, zona incerta and PFA. Termed ‘hypocretins 1 and 2’83 or ‘orexins A and B’84 by the two groups that simultaneously discovered them, these peptides increase food intake and cause generalized behavioural arousal when administered centrally84,85. Targeted deletion of the hypocretin/orexin gene in mice induces narcolepsy86, a disorder characterized by the sudden onset of sleep at times when it would not ordinarily occur. This finding indicates that reduced hypocretin/orexinsignallingmaycontributetotheonsetandmaintenanceof sleep, in addition to its potential role in the control of food intake. Integration of MCH and hypocretin/orexin neurons into a model of the hypothalamic pathways controlling energy homeostasis predicts that they should be inhibited by melanocortin or CART input, and stimulated by NPY signalling, from neurons of the arcuate nucleus. Much work must be done to test this model of first- and secondorder neurons in the energy homeostasis circuit. Identifying specific neuronal subsets in the PVN and LHA that express NPY and melanocortin receptors is an important priority. Because many neurons of the PVN, PFA and LHA project to the arcuate nucleus, neuronal traffic flows bidirectionally between the arcuate nucleus and these other hypothalamic sites. So rather than being passive recipients of information from the arcuate nucleus, these secondorder neurons can actively modify the information that arrives there. In addition, leptin receptors have been described on PVN and LHA neurons,implicatingthemasdirecttargetsforregulationbycirculating adiposity signals.