Open AccessHuman aquaporin adipose (AQPap) gene
Author(s) -
Kondo Hidehiko,
Shimomura Iichiro,
Kishida Ken,
Kuriyama Hiroshi,
Makino Yasunaka,
Nishizawa Hitoshi,
Matsuda Morihiro,
Maeda Norikazu,
Nagaretani Hiroyuki,
Kihara Shinji,
Kurachi Yoshihisa,
Nakamura Tadashi,
Funahashi Tohru,
Matsuzawa Yuji
Publication year - 2002
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2002.02821.x
Subject(s) - adipose tissue , adipocyte , gene , biology , mutant , missense mutation , microbiology and biotechnology , mutation , endocrinology , genetics
Aquaporin adipose (AQPap), which we identified from human adipose tissue, is a glycerol channel in adipocyte [Kishida et al . (2000) J. Biol. Chem. 275 , 20896–20902]. In the current study, we determined the genomic structure of the human AQPap gene, and identified three AQPap‐like genes that resembled (≈ 95%) AQPap, with little expression in human tissues. The AQPap promoter contained a putative peroxisome proliferator response element (PPRE) at −46 to −62, and a putative insulin response element (IRE) at −542/−536. Deletion of the PPRE abolished the pioglitazone‐mediated induction of AQPap promoter activity in 3T3‐L1 adipocytes. Deletion and single base pair substitution analysis of the IRE abolished the insulin‐mediated suppression of the human AQPap gene. Analysis of AQPap sequence in human subjects revealed three missense mutations (R12C, V59L and G264V), and two silent mutations (A103A and G250G). The cRNA injection of the missense mutants into Xenopus oocytes revealed the absence of the activity to transport glycerol and water in the AQPap‐G264V protein. In the subject homozygous for AQPap‐G264V, exercise‐induced increase in plasma glycerol was not observed in spite of the increased plasma noradrenaline. We suggest that AQPap is responsible for the increase of plasma glycerol during exercise in humans.