unpublished data), suggesting that glucagon and insulin also exert opposite effects onleptingene expression in this Cyprinidae species

unpublished data), suggesting that glucagon and insulin also exert opposite effects onleptingene expression in this Cyprinidae species. in the fish model. Keywords: leptin, glucagon, gene expression, signal transduction, goldfish. == Introduction == Leptin, the protein product of theobesegene1, is one of the most prominent corpulence tissue-derived hormones and plays a key role in the regulation of appetite and metabolism in vertebrates ranging from fish to mammals2-4. In mammals, the adipose mRNA and serum protein levels of leptin are positively correlated with body corpulence mass5, 6. The mammalian serum leptin levels are decreased prior to the depletion of adipose tissue mass by fasting7, rapidly restored by re-feeding8, and increased by overfeeding9. A number of peptide and non-peptide hormones have been found to mediate leptin production and secretion in mammalian models. Cholecystokinin10and ghrelin11, two gastrointestinal appetite-regulated hormones, are effective at stimulating leptin secretion in rats. The sexual steroid hormones estrogen and androgen may play opposite roles, which are positive and negative, respectively, in the regulation of leptin gene expression in rat fat cells12and human placental cells13. In addition , insulin is another major stimulator of leptin production and secretion in rat and mouse adipocytes14, 15, while its homologous hormone insulin-like growth factor-I (IGF-I) may suppress leptin secretion in rats16. PF-5006739 The anorexigenic effects of leptin have been described in teleost fish17, 18as well as in mammals19. The nutritional status is shown highly correlated to leptin levels in fish but controversial between different species4. Following food deprivation, the plasma leptin content and/or hepaticleptintranscript levels are elevated in rainbow trout20, salmon21, flounder22, grouper23and minnows24. Re-feeding may rapidly eliminate the up-regulation of leptin protein and/or mRNA levels in flounder22, grouper23and minnows24that is caused by starvation. In contrast, neither short- nor long-term fasting nor subsequent re-feeding affected the hepaticleptinexpression in common carp25, and the hepaticleptinmRNA level increased at a long time after feeding in goldfish26. However , the regulatory mediator that links the nutritional status and leptin level in fish is still unclear. Glucagon is a key metabolism-regulated hormone that is produced in -cells of the pancreas in mammals. It works to raise the concentration of glucose in plasma, and PF-5006739 its effect is opposite to that of insulin, which lowers the circulating glucose levels27. During fasting, glucagon is a primary regulator of hepatic glucose production and release27. Theproglucagon28andglucagon receptor29cDNAs have been previously identified in goldfish. Glucagon is effective at the stimulation of glucose production in goldfish hepatocytes, and both goldfish and human glucagons can bind the PF-5006739 goldfish glucagon receptor and activate its intracellular signal pathways29. In mammalian and non-mammalian species, glucagon can regulate the production and/or secretion of other hormones, e. g., ghrelin in rats30, somatostatin in rainbow trout31and fibroblast growth factor in rats32. However , as reported in sheep, glucagon has no effects on blood leptin levels33, 34. To our knowledge, the effect of glucagon on leptin regulation HSPC150 in fish has not yet been examined previously. Phylogenetically, the aspect ofleptingenes in teleost fish is more complicated than that in mammals4, 35. This is partially due to the fish-specific genome duplication (FSGD or 3R) that occurred in teleosts36; duplicatedleptingenes (leptin-A andleptin-B) have been reported in some fish species, whereas only a singleleptingene is found in mammals1, 4, 37. The receptor binding affinity of fish leptin-A is higher than that of leptin-B38, 39, indicating that leptin-A is the dominant form of leptin in fish. Moreover, another genome duplication event, also called tetraploidization, in cyprinids25and salmonids40resulted in up to fourleptinparalogs in these species. In goldfish, twoleptingenes (GenBank: FJ534535andFJ854572) have been reported. They are both phylogenetically clustered with other Cyprinidaeleptin-A and therefore named goldfishleptin-AI andleptin-AII, respectively26, 41. However , theleptin-B has not yet been reported in goldfish. Recombinant goldfish leptin-AI and leptin-AII protein were effective at inhibiting feeding behavior and reducing food PF-5006739 consumption of goldfish via mediating of the transcript levels of some central appetite regulators17. The liver is the metabolic center in fish, and it is also the major site for leptin expression in fish25, 42. To date, studies on the hormonal regulation of leptin in fish remain limited, except for finding that prolactin suppresses leptin-A synthesis in tilapia43, and the estrogen stimulatesleptin-A gene expression in minnows24. To shed light on the regulatory mechanism of leptin in.