Elucidation of pbysiological significance in the fat-derived molecules with those expressions regulated by feeding and the importance of those molecules in the development of life-style related disease.

我们制作了人类脂肪组织中表达的基因图谱，并利用该图谱克隆了仅在脂肪组织中表达的新基因。脂肪组织中高表达的基因，其表达因喂养而发生显著变化，换言之，受许多营养调节影响的基因可能与包括肥胖在内的生活方式相关疾病的发展密切相关。脂肪水通道蛋白（AQPap）和新克隆的空腹诱导蛋白（FIP）在脂肪组织中均有高表达，且空腹后表达量显著增加。我们报道了AQPap在脂肪细胞中作为甘油通道，AQPap是机体甘油代谢的关键分子之一，并且AQPap基因敲除小鼠表现为肥胖。在目前的研究期间，我们试图利用AQPap基因敲除小鼠来研究心脏中的甘油代谢以及AQPap在该器官中的作用。我们证实AQPap在小鼠心脏和脂肪组织中均有表达，然后我们发现AQPap基因敲除小鼠出现心肌肥大。此外，该基因敲除小鼠心脏对甘油的摄取减少，表明该基因敲除小鼠可能存在一些基于甘油代谢的心脏代谢紊乱。对于另一个基因FIP，我们在细胞和动物实验中发现胰岛素对FIP mRNA的表达有负调控作用。构建FIP腺病毒，研究FIP对糖代谢的影响。静脉注射FIP腺病毒可显著降低正常小鼠在葡萄糖负荷和餐后状态下的血糖水平，提示FIP可能在葡萄糖代谢中发挥重要作用。因此，这两种分子的研究结果可能会对代谢研究的进展做出更多的贡献。

We made a profile of the genes expressed in human adipose tissue and have performed cloning of novel genes expressed exclusively in adipose tissue with this profile. The highly expressed genes in adipose tissue with those expression dramatically changed by feeding, in other words, the genes influenced by a lot of nutritional regulation might be involved strongly in the development of life-style related disease including obesity. Aquaporin adipose (AQPap) and a newly cloned gene, Fasting induced protein (FIP) were both expressed highly in adipose tissue and those expressions were much increased by fasting. We reported that AQPap acts as a glycerol channel in adipocytes and that AQPap is one of the key molecules in glycerol metabolism of the body and that AQPap knockout mice show obesity. Within the current research duration, we tried to investigate the glycerol metabolism in heart and the role of AQPap in this organ using AQPap knockout mice. We confirmed that AQPap was expressed in hearts of mice as well as adipose tissue and then we found out AQPap knockout mice showed cardiac hypertrophy. Moreover, the uptake of glycerol by heart was reduced in this knockout mice, suggesting that some metabolic disorders in heart based on glycerol metabolism could exist in this knockout mice.For another gene FIP, we found out that FIP mRNA expression is negatively regulated by insulin on the cell and animal studies. We constructed FIP adenovirus and investigated the effect of FIP on glucose metabolism. The administration of FIP adenovirus into vein significantly decreased blood glucose levels of the regular mice in the glucose-loading and postprandial state, suggesting that FIP could play an important role in glucose metabolism.Thus, the research results for these both molecules might be able to contribute more to the progress of metabolism study.