Clarification of the physiological mechanism in a novel adipose specific glycerol channel discovered by us

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Aquaporin adipose (AQPap) is an adipose-specific glycerol channel. We identified the peroxisome proliferator response element (PPRE) activated receptor in the promoter region of mouse AQPap gene. Binding and activation of peroxisome proliferator activated receptor γ (PPARγ) to this element was suggested to explain the adipose-specific expression of AQPap mRNA.AQPap gene expression was negatively regulated by insulin in vivo and in tissue cultures. In the analysis of AQPap promoter, we showed there was an insulin negative response element composed of seven nucleotides.In the search of genetic mutations of AQPap in 160 human subjects, we found three different types of missense mutation (R12C, V59L, G264V) and two types of silent mutations (A103A, G250G). By the functional analysis, the G264V-type AQPap was not capable of transporting glycerol using the xenopus oocyte system. The homozygous subject far G264V AQPap failed to raise the concentrations of plasma glycerol in response to vigorous exercise, while there was an equivalent serge of plasma noradrenalin, suggesting that the AQPap is mediating the glycerol release from adipose tissues by exercise in human.We are now investigating the phenotypes of AQPap knockout mice to clarify the physiological significance of AQPap and glycerol metabolism in whole body.