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.

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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.