Advertisement

Cellular and Molecular Life Sciences

, Volume 72, Issue 4, pp 759–771 | Cite as

Aquaglyceroporins: implications in adipose biology and obesity

  • Ana Madeira
  • Teresa F. Moura
  • Graça Soveral
Review

Abstract

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological processes. Their primary function is to facilitate the bidirectional transfer of water and small solutes across biological membranes in response to osmotic gradients. Aquaglyceroporins, a subset of the AQP family, are the only mammalian proteins with the ability to permeate glycerol. For a long time, AQP7 has been the only aquaglyceroporin associated with the adipose tissue, which is the major source of circulating glycerol in response to the energy demand. AQP7 dysregulation was positively correlated with obesity onset and adipocyte glycerol permeation through AQP7 was appointed as a novel regulator of adipocyte metabolism and whole-body fat mass. Recently, AQP3, AQP9, AQP10 and AQP11 were additionally identified in human adipocytes and proposed as additional glycerol pathways in these cells. This review contextualizes the importance of aquaglyceroporins in adipose tissue biology and highlights aquaglyceroporins’ unique structural features which are relevant for the design of effective therapeutic compounds. We also refer to the latest advances in the identification and characterization of novel aquaporin isoforms in adipose tissue. Finally, considerations on the actual progress of aquaporin research and its implications on obesity therapy are suggested.

Keywords

Aquaporin Adipocyte Obesity Diabetes Membrane permeability 

Notes

Acknowledgments

We thank Fundação para a Ciência e Tecnologia FCT-MCTES, Portugal, for fellowship (SFRH/BD/45930/2008) to A. Madeira.

References

  1. 1.
    Virtue S, Vidal-Puig A (2010) Adipose tissue expandability, lipotoxicity and the Metabolic syndrome—an allostatic perspective. Biochim Biophys Acta 1801(3):338–349. doi: 10.1016/j.bbalip.2009.12.006 PubMedGoogle Scholar
  2. 2.
    Tchernof A, Despres JP (2013) Pathophysiology of human visceral obesity: an update. Physiol Rev 93(1):359–404. doi: 10.1152/physrev.00033.2011 PubMedGoogle Scholar
  3. 3.
    Frayn KN (2002) Adipose tissue as a buffer for daily lipid flux. Diabetologia 45(9):1201–1210. doi: 10.1007/s00125-002-0873-y PubMedGoogle Scholar
  4. 4.
    Gray SL, Vidal-Puig AJ (2007) Adipose tissue expandability in the maintenance of metabolic homeostasis. Nutr Rev 65(6 Pt 2):S7–S12PubMedGoogle Scholar
  5. 5.
    Lafontan M (2013) Adipose tissue and adipocyte dysregulation. Diabetes Metab. doi: 10.1016/j.diabet.2013.08.002 PubMedGoogle Scholar
  6. 6.
    Fruhbeck G (2005) Obesity: aquaporin enters the picture. Nature 438(7067):436–437. doi: 10.1038/438436b PubMedGoogle Scholar
  7. 7.
    Maeda N (2012) Implications of aquaglyceroporins 7 and 9 in glycerol metabolism and metabolic syndrome. Mol Aspects Med 33(5–6):665–675. doi: 10.1016/j.mam.2012.02.004 PubMedGoogle Scholar
  8. 8.
    Lin EC (1977) Glycerol utilization and its regulation in mammals. Annu Rev Biochem 46:765–795. doi: 10.1146/annurev.bi.46.070177.004001 PubMedGoogle Scholar
  9. 9.
    Rodriguez A, Catalan V, Gomez-Ambrosi J, Fruhbeck G (2011) Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control. Cell Cycle 10(10):1548–1556 (15672 [pii])PubMedCentralPubMedGoogle Scholar
  10. 10.
    Ballard FJ, Hanson RW, Leveille GA (1967) Phosphoenolpyruvate carboxykinase and the synthesis of glyceride-glycerol from pyruvate in adipose tissue. J Biol Chem 242(11):2746–2750PubMedGoogle Scholar
  11. 11.
    Gorin E, Tal-Or Z, Shafrir E (1969) Glyceroneogenesis in adipose tissue of fasted, diabetic and triamcinolone treated rats. Eur J Biochem 8(3):370–375PubMedGoogle Scholar
  12. 12.
    Reshef L, Olswang Y, Cassuto H, Blum B, Croniger CM, Kalhan SC, Tilghman SM, Hanson RW (2003) Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem 278(33):30413–30416. doi: 10.1074/jbc.R300017200 PubMedGoogle Scholar
  13. 13.
    Carlson LA, Ostman J (1963) In vitro studies on the glucose uptake and fatty acid metabolism of human adipose tissue in diabetes mellitus. A preliminary report. Acta Med Scand 174:215–218PubMedGoogle Scholar
  14. 14.
    Ostman J (1965) Studies in vitro on fatty acid metabolism of human subcutaneous adipose tissue in diabetes mellitus. Acta Med Scand 177:639–655PubMedGoogle Scholar
  15. 15.
    Pelkonen R, Nikkila EA, Kekki M (1967) Metabolism of glycerol in diabetes mellitus. Diabetologia 3(1):1–8PubMedGoogle Scholar
  16. 16.
    Nurjhan N, Consoli A, Gerich J (1992) Increased lipolysis and its consequences on gluconeogenesis in non-insulin-dependent diabetes mellitus. J Clin Invest 89(1):169–175. doi: 10.1172/JCI115558 PubMedCentralPubMedGoogle Scholar
  17. 17.
    Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC (1996) Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Investig 98(2):378–385PubMedCentralPubMedGoogle Scholar
  18. 18.
    Coppack SW, Persson M, Judd RL, Miles JM (1999) Glycerol and nonesterified fatty acid metabolism in human muscle and adipose tissue in vivo. Am J Physiol 276(2 Pt 1):E233–E240PubMedGoogle Scholar
  19. 19.
    Bortz WM, Paul P, Haff AC, Holmes WL (1972) Glycerol turnover and oxidation in man. J Clin Invest 51(6):1537–1546. doi: 10.1172/JCI106950 PubMedCentralPubMedGoogle Scholar
  20. 20.
    Carlson MG, Snead WL, Campbell PJ (1994) Fuel and energy metabolism in fasting humans. Am J Clin Nutr 60(1):29–36PubMedGoogle Scholar
  21. 21.
    Nordlander S, Ostman J, Cerasi E, Luft R, Ekelund LG (1973) Occurrence of diabetic type of plasma FFA and glycerol responses to physical exercise in prediabetic subjects. Acta Med Scand 193(1–2):9–21PubMedGoogle Scholar
  22. 22.
    Jansson PA, Larsson A, Smith U, Lonnroth P (1992) Glycerol production in subcutaneous adipose tissue in lean and obese humans. J Clin Invest 89(5):1610–1617. doi: 10.1172/JCI115756 PubMedCentralPubMedGoogle Scholar
  23. 23.
    Hagen JH (1963) The effect of insulin on concentration of plasma glycerol. J Lipid Res 4:46–51PubMedGoogle Scholar
  24. 24.
    Thompson BR, Lobo S, Bernlohr DA (2010) Fatty acid flux in adipocytes: the in’s and out’s of fat cell lipid trafficking. Mol Cell Endocrinol 318(1–2):24–33. doi: 10.1016/j.mce.2009.08.015 PubMedCentralPubMedGoogle Scholar
  25. 25.
    Rojek A, Praetorius J, Frokiaer J, Nielsen S, Fenton RA (2008) A current view of the mammalian aquaglyceroporins. Annu Rev Physiol 70:301–327. doi: 10.1146/annurev.physiol.70.113006.100452 PubMedGoogle Scholar
  26. 26.
    Tornroth-Horsefield S, Hedfalk K, Fischer G, Lindkvist-Petersson K, Neutze R (2010) Structural insights into eukaryotic aquaporin regulation. FEBS Lett 584(12):2580–2588. doi: 10.1016/j.febslet.2010.04.037 PubMedGoogle Scholar
  27. 27.
    Preston GM, Carroll TP, Guggino WB, Agre P (1992) Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 256(5055):385–387PubMedGoogle Scholar
  28. 28.
    Agre P (2004) Aquaporin water channels (Nobel lecture). Angew Chem Int Ed 43:4278–4290Google Scholar
  29. 29.
    Carbrey JM, Agre P (2009) Discovery of the aquaporins and development of the field. Handb Exp Pharmacol 190:3–28. doi: 10.1007/978-3-540-79885-9_1 PubMedGoogle Scholar
  30. 30.
    Ishibashi K, Hara S, Kondo S (2009) Aquaporin water channels in mammals. Clin Exp Nephrol 13(2):107–117. doi: 10.1007/s10157-008-0118-6 PubMedGoogle Scholar
  31. 31.
    Alleva K, Chara O, Amodeo G (2012) Aquaporins: another piece in the osmotic puzzle. FEBS Lett 586(19):2991–2999. doi: 10.1016/j.febslet.2012.06.013 PubMedGoogle Scholar
  32. 32.
    Tanghe A, Van Dijck P, Thevelein JM (2006) Why do microorganisms have aquaporins? Trends Microbiol 14(2):78–85. doi: 10.1016/j.tim.2005.12.001 PubMedGoogle Scholar
  33. 33.
    Soveral G, Prista C, Moura TF, Loureiro-Dias MC (2011) Yeast water channels: an overview of orthodox aquaporins. Biol Cell 103(1):35–54. doi: 10.1042/BC20100102 Google Scholar
  34. 34.
    Maurel C, Reizer J, Schroeder JI, Chrispeels MJ, Saier MH Jr (1994) Functional characterization of the Escherichia coli glycerol facilitator, GlpF. Xenopus oocytes. J Biol Chem 269(16):11869–11872Google Scholar
  35. 35.
    Calamita G, Bishai WR, Preston GM, Guggino WB, Agre P (1995) Molecular cloning and characterization of AqpZ, a water channel from Escherichia coli. J Biol Chem 270(49):29063–29066PubMedGoogle Scholar
  36. 36.
    Maurel C, Verdoucq L, Luu DT, Santoni V (2008) Plant aquaporins: membrane channels with multiple integrated functions. Annu Rev Plant Biol 59:595–624. doi: 10.1146/annurev.arplant.59.032607.092734 PubMedGoogle Scholar
  37. 37.
    Verkman AS (2009) Aquaporins: translating bench research to human disease. J Exp Biol 212(Pt 11):1707–1715. doi: 10.1242/jeb.024125 PubMedCentralPubMedGoogle Scholar
  38. 38.
    Ishibashi K, Tanaka Y, Morishita Y (2014) The role of mammalian superaquaporins inside the cell. Biochim Biophys Acta 1840(5):1507–1512. doi: 10.1016/j.bbagen.2013.10.039 PubMedGoogle Scholar
  39. 39.
    Verkman AS, Anderson MO, Papadopoulos MC (2014) Aquaporins: important but elusive drug targets. Nat Rev Drug Discov 13(4):259–277. doi: 10.1038/nrd4226 PubMedGoogle Scholar
  40. 40.
    Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (2000) Structural determinants of water permeation through aquaporin-1. Nature 407(6804):599–605. doi: 10.1038/35036519 PubMedGoogle Scholar
  41. 41.
    Lee JK, Kozono D, Remis J, Kitagawa Y, Agre P, Stroud RM (2005) Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 A. Proc Natl Acad Sci USA 102(52):18932–18937. doi: 10.1073/pnas.0509469102 PubMedCentralPubMedGoogle Scholar
  42. 42.
    Fu D, Libson A, Miercke LJ, Weitzman C, Nollert P, Krucinski J, Stroud RM (2000) Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290(5491):481–486 (8914 [pii])PubMedGoogle Scholar
  43. 43.
    Savage DF, Egea PF, Robles-Colmenares Y, O’Connell JD 3rd, Stroud RM (2003) Architecture and selectivity in aquaporins: 2.5 a X-ray structure of aquaporin Z. PLoS Biol 1(3):E72. doi: 10.1371/journal.pbio.0000072 PubMedCentralPubMedGoogle Scholar
  44. 44.
    Fischer G, Kosinska-Eriksson U, Aponte-Santamaria C, Palmgren M, Geijer C, Hedfalk K, Hohmann S, de Groot BL, Neutze R, Lindkvist-Petersson K (2009) Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism. PLoS Biol 7(6):e1000130. doi: 10.1371/journal.pbio.1000130 PubMedCentralPubMedGoogle Scholar
  45. 45.
    Newby ZE, O’Connell J 3rd, Robles-Colmenares Y, Khademi S, Miercke LJ, Stroud RM (2008) Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nat Struct Mol Biol 15(6):619–625. doi: 10.1038/nsmb.1431 PubMedCentralPubMedGoogle Scholar
  46. 46.
    Tornroth-Horsefield S, Wang Y, Hedfalk K, Johanson U, Karlsson M, Tajkhorshid E, Neutze R, Kjellbom P (2006) Structural mechanism of plant aquaporin gating. Nature 439(7077):688–694. doi: 10.1038/nature04316 PubMedGoogle Scholar
  47. 47.
    Sui H, Han BG, Lee JK, Walian P, Jap BK (2001) Structural basis of water-specific transport through the AQP1 water channel. Nature 414(6866):872–878. doi: 10.1038/414872a PubMedGoogle Scholar
  48. 48.
    Harries WE, Akhavan D, Miercke LJ, Khademi S, Stroud RM (2004) The channel architecture of aquaporin 0 at a 2.2-A resolution. Proc Natl Acad Sci USA 101(39):14045–14050. doi: 10.1073/pnas.0405274101 PubMedCentralPubMedGoogle Scholar
  49. 49.
    Gonen T, Cheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, Walz T (2005) Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. Nature 438(7068):633–638. doi: 10.1038/nature04321 PubMedCentralPubMedGoogle Scholar
  50. 50.
    Horsefield R, Norden K, Fellert M, Backmark A, Tornroth-Horsefield S, Terwisscha van Scheltinga AC, Kvassman J, Kjellbom P, Johanson U, Neutze R (2008) High-resolution x-ray structure of human aquaporin 5. Proc Natl Acad Sci USA 105(36):13327–13332. doi: 10.1073/pnas.0801466105 PubMedCentralPubMedGoogle Scholar
  51. 51.
    Hub JS, Grubmuller H, de Groot BL (2009) Dynamics and energetics of permeation through aquaporins. What do we learn from molecular dynamics simulations? Handb Exp Pharmacol 190:57–76. doi: 10.1007/978-3-540-79885-9_3 PubMedGoogle Scholar
  52. 52.
    Smith BL, Agre P (1991) Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins. J Biol Chem 266(10):6407–6415PubMedGoogle Scholar
  53. 53.
    Preston GM, Jung JS, Guggino WB, Agre P (1993) The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel. J Biol Chem 268(1):17–20PubMedGoogle Scholar
  54. 54.
    Jung JS, Preston GM, Smith BL, Guggino WB, Agre P (1994) Molecular structure of the water channel through aquaporin CHIP. The hourglass model. J Biol Chem 269(20):14648–14654PubMedGoogle Scholar
  55. 55.
    Wang Y, Cohen J, Boron WF, Schulten K, Tajkhorshid E (2007) Exploring gas permeability of cellular membranes and membrane channels with molecular dynamics. J Struct Biol 157(3):534–544. doi: 10.1016/j.jsb.2006.11.008 PubMedGoogle Scholar
  56. 56.
    Hub JS, de Groot BL (2008) Mechanism of selectivity in aquaporins and aquaglyceroporins. Proc Natl Acad Sci USA 105(4):1198–1203. doi: 10.1073/pnas.0707662104 PubMedCentralPubMedGoogle Scholar
  57. 57.
    Wang Y, Tajkhorshid E (2010) Nitric oxide conduction by the brain aquaporin AQP4. Proteins 78(3):661–670. doi: 10.1002/prot.22595 PubMedCentralPubMedGoogle Scholar
  58. 58.
    Yool AJ, Weinstein AM (2002) New roles for old holes: ion channel function in aquaporin-1. News Physiol Sci 17:68–72PubMedGoogle Scholar
  59. 59.
    Boassa D, Stamer WD, Yool AJ (2006) Ion channel function of aquaporin-1 natively expressed in choroid plexus. J Neurosci 26(30):7811–7819. doi: 10.1523/JNEUROSCI.0525-06.2006 PubMedGoogle Scholar
  60. 60.
    Preston GM, Agre P (1991) Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family. Proc Natl Acad Sci USA 88(24):11110–11114PubMedCentralPubMedGoogle Scholar
  61. 61.
    Tani K, Fujiyoshi Y (2014) Water channel structures analysed by electron crystallography. Biochim Biophys Acta 1840(5):1605–1613. doi: 10.1016/j.bbagen.2013.10.007 PubMedGoogle Scholar
  62. 62.
    Mitsuoka K, Murata K, Walz T, Hirai T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (1999) The structure of aquaporin-1 at 4.5-A resolution reveals short alpha-helices in the center of the monomer. J Struct Biol 128(1):34–43. doi: 10.1006/jsbi.1999.4177 PubMedGoogle Scholar
  63. 63.
    de Groot BL, Grubmuller H (2001) Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294(5550):2353–2357. doi: 10.1126/science.1062459 PubMedGoogle Scholar
  64. 64.
    Walz T, Fujiyoshi Y, Engel A (2009) The AQP structure and functional implications. Handb Exp Pharmacol 190:31–56. doi: 10.1007/978-3-540-79885-9_2 PubMedGoogle Scholar
  65. 65.
    Tajkhorshid E, Nollert P, Jensen MO, Miercke LJ, O’Connell J, Stroud RM, Schulten K (2002) Control of the selectivity of the aquaporin water channel family by global orientational tuning. Science 296(5567):525–530. doi: 10.1126/science.1067778 PubMedGoogle Scholar
  66. 66.
    Borgnia MJ, Agre P (2001) Reconstitution and functional comparison of purified GlpF and AqpZ, the glycerol and water channels from Escherichia coli. Proc Natl Acad Sci USA 98(5):2888–2893. doi: 10.1073/pnas.051628098 PubMedCentralPubMedGoogle Scholar
  67. 67.
    Wang Y, Schulten K, Tajkhorshid E (2005) What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF. Structure 13(8):1107–1118. doi: 10.1016/j.str.2005.05.005 PubMedGoogle Scholar
  68. 68.
    Martins AP, Marrone A, Ciancetta A, Galan Cobo A, Echevarria M, Moura TF, Re N, Casini A, Soveral G (2012) Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound. PLoS One 7(5):e37435. doi: 10.1371/journal.pone.0037435 PubMedCentralPubMedGoogle Scholar
  69. 69.
    Madeira A, de Almeida A, de Graaf C, Camps M, Zorzano A, Moura TF, Casini A, Soveral G (2014) A gold coordination compound as a chemical probe to unravel aquaporin-7 function. Chembiochem 15(10):1487–1494. doi: 10.1002/cbic.201402103 PubMedGoogle Scholar
  70. 70.
    Ishibashi K, Kuwahara M, Gu Y, Kageyama Y, Tohsaka A, Suzuki F, Marumo F, Sasaki S (1997) Cloning and functional expression of a new water channel abundantly expressed in the testis permeable to water, glycerol, and urea. J Biol Chem 272(33):20782–20786PubMedGoogle Scholar
  71. 71.
    Ishibashi K, Yamauchi K, Kageyama Y, Saito-Ohara F, Ikeuchi T, Marumo F, Sasaki S (1998) Molecular characterization of human Aquaporin-7 gene and its chromosomal mapping. Biochim Biophys Acta 1399(1):62–66 (S0167-4781(98)00094-3 [pii])PubMedGoogle Scholar
  72. 72.
    Kishida K, Kuriyama H, Funahashi T, Shimomura I, Kihara S, Ouchi N, Nishida M, Nishizawa H, Matsuda M, Takahashi M, Hotta K, Nakamura T, Yamashita S, Tochino Y, Matsuzawa Y (2000) Aquaporin adipose, a putative glycerol channel in adipocytes. J Biol Chem 275(27):20896–20902PubMedGoogle Scholar
  73. 73.
    Madeira A, Camps M, Zorzano A, Moura TF, Soveral G (2013) Biophysical assessment of human aquaporin-7 as a water and glycerol channel in 3T3-L1 adipocytes. PLoS One 8(12):e83442PubMedCentralPubMedGoogle Scholar
  74. 74.
    Fain JN, Buehrer B, Bahouth SW, Tichansky DS, Madan AK (2008) Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue. Metabolism 57(7):1005–1015. doi: 10.1016/j.metabol.2008.02.019 PubMedGoogle Scholar
  75. 75.
    Miranda M, Escote X, Ceperuelo-Mallafre V, Alcaide MJ, Simon I, Vilarrasa N, Wabitsch M, Vendrell J (2010) Paired subcutaneous and visceral adipose tissue aquaporin-7 expression in human obesity and type 2 diabetes: differences and similarities between depots. J Clin Endocrinol Metab 95(7):3470–3479. doi: 10.1210/jc.2009-2655 PubMedGoogle Scholar
  76. 76.
    Rodriguez A, Catalan V, Gomez-Ambrosi J, Garcia-Navarro S, Rotellar F, Valenti V, Silva C, Gil MJ, Salvador J, Burrell MA, Calamita G, Malagon MM, Fruhbeck G (2011) Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade. J Clin Endocrinol Metab 96(4):E586–E597. doi: 10.1210/jc.2010-1408 PubMedGoogle Scholar
  77. 77.
    Skowronski MT, Lebeck J, Rojek A, Praetorius J, Fuchtbauer EM, Frokiaer J, Nielsen S (2007) AQP7 is localized in capillaries of adipose tissue, cardiac and striated muscle: implications in glycerol metabolism. Am J Physiol Renal Physiol 292(3):F956–F965. doi: 10.1152/ajprenal.00314.2006 PubMedGoogle Scholar
  78. 78.
    Lebeck J, Ostergard T, Rojek A, Fuchtbauer EM, Lund S, Nielsen S, Praetorius J (2012) Gender-specific effect of physical training on AQP7 protein expression in human adipose tissue. Acta Diabetol 49(Suppl 1):S215–S226. doi: 10.1007/s00592-012-0430-1 PubMedGoogle Scholar
  79. 79.
    Kuriyama H, Shimomura I, Kishida K, Kondo H, Furuyama N, Nishizawa H, Maeda N, Matsuda M, Nagaretani H, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y (2002) Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9. Diabetes 51(10):2915–2921PubMedGoogle Scholar
  80. 80.
    Lee DH, Park DB, Lee YK, An CS, Oh YS, Kang JS, Kang SH, Chung MY (2005) The effects of thiazolidinedione treatment on the regulations of aquaglyceroporins and glycerol kinase in OLETF rats. Metabolism 54(10):1282–1289. doi: 10.1016/j.metabol.2005.04.015 PubMedGoogle Scholar
  81. 81.
    Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, Uchida S, Verkman AS (2005) Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 280(16):15493–15496PubMedGoogle Scholar
  82. 82.
    Hibuse T, Maeda N, Funahashi T, Yamamoto K, Nagasawa A, Mizunoya W, Kishida K, Inoue K, Kuriyama H, Nakamura T, Fushiki T, Kihara S, Shimomura I (2005) Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci USA 102(31):10993–10998PubMedCentralPubMedGoogle Scholar
  83. 83.
    Verkman AS (2012) Aquaporins in clinical medicine. Annu Rev Med 63:303–316. doi: 10.1146/annurev-med-043010-193843 PubMedCentralPubMedGoogle Scholar
  84. 84.
    Fruhbeck G, Catalan V, Gomez-Ambrosi J, Rodriguez A (2006) Aquaporin-7 and glycerol permeability as novel obesity drug-target pathways. Trends Pharmacol Sci 27(7):345–347PubMedGoogle Scholar
  85. 85.
    Matsumura K, Chang BH, Fujimiya M, Chen W, Kulkarni RN, Eguchi Y, Kimura H, Kojima H, Chan L (2007) Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion. Mol Cell Biol 27(17):6026–6037. doi: 10.1128/MCB.00384-07 PubMedCentralPubMedGoogle Scholar
  86. 86.
    Lindgren CM, Mahtani MM, Widen E, McCarthy MI, Daly MJ, Kirby A, Reeve MP, Kruglyak L, Parker A, Meyer J, Almgren P, Lehto M, Kanninen T, Tuomi T, Groop LC, Lander ES (2002) Genomewide search for type 2 diabetes mellitus susceptibility loci in Finnish families: the Botnia study. Am J Hum Genet 70(2):509–516. doi: 10.1086/338629 PubMedCentralPubMedGoogle Scholar
  87. 87.
    Loos RJ, Katzmarzyk PT, Rao DC, Rice T, Leon AS, Skinner JS, Wilmore JH, Rankinen T, Bouchard C (2003) Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study. J Clin Endocrinol Metab 88(12):5935–5943PubMedGoogle Scholar
  88. 88.
    Prudente S, Flex E, Morini E, Turchi F, Capponi D, De Cosmo S, Tassi V, Guida V, Avogaro A, Folli F, Maiani F, Frittitta L, Dallapiccola B, Trischitta V (2007) A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities. Diabetes 56(5):1468–1474PubMedGoogle Scholar
  89. 89.
    Kondo H, Shimomura I, Kishida K, Kuriyama H, Makino Y, Nishizawa H, Matsuda M, Maeda N, Nagaretani H, Kihara S, Kurachi Y, Nakamura T, Funahashi T, Matsuzawa Y (2002) Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation. Eur J Biochem 269(7):1814–1826 (2821 [pii])PubMedGoogle Scholar
  90. 90.
    Goubau C, Jaeken J, Levtchenko EN, Thys C, Di Michele M, Martens GA, Gerlo E, De Vos R, Buyse GM, Goemans N, Van Geet C, Freson K (2013) Homozygosity for aquaporin 7 G264V in three unrelated children with hyperglyceroluria and a mild platelet secretion defect. Genet Med 15(1):55–63. doi: 10.1038/gim.2012.90 PubMedGoogle Scholar
  91. 91.
    Ceperuelo-Mallafre V, Miranda M, Chacon MR, Vilarrasa N, Megia A, Gutierrez C, Fernandez-Real JM, Gomez JM, Caubet E, Fruhbeck G, Vendrell J (2007) Adipose tissue expression of the glycerol channel aquaporin-7 gene is altered in severe obesity but not in type 2 diabetes. J Clin Endocrinol Metab 92(9):3640–3645PubMedGoogle Scholar
  92. 92.
    Mendez-Gimenez L, Rodriguez A, Balaguer I, Fruhbeck G (2014) Role of aquaglyceroporins and caveolins in energy and metabolic homeostasis. Mol Cell Endocrinol. doi: 10.1016/j.mce.2014.06.017 PubMedGoogle Scholar
  93. 93.
    Cristancho AG, Lazar MA (2011) Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12(11):722–734. doi: 10.1038/nrm3198 PubMedGoogle Scholar
  94. 94.
    Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444(7121):840–846PubMedGoogle Scholar
  95. 95.
    Catalan V, Gomez-Ambrosi J, Pastor C, Rotellar F, Silva C, Rodriguez A, Gil MJ, Cienfuegos JA, Salvador J, Vendrell J, Fruhbeck G (2008) Influence of morbid obesity and insulin resistance on gene expression levels of AQP7 in visceral adipose tissue and AQP9 in liver. Obes Surg 18(6):695–701. doi: 10.1007/s11695-008-9453-7 PubMedGoogle Scholar
  96. 96.
    Miranda M, Ceperuelo-Mallafre V, Lecube A, Hernandez C, Chacon MR, Fort JM, Gallart L, Baena-Fustegueras JA, Simo R, Vendrell J (2009) Gene expression of paired abdominal adipose AQP7 and liver AQP9 in patients with morbid obesity: relationship with glucose abnormalities. Metabolism 58(12):1762–1768. doi: 10.1016/j.metabol.2009.06.004 PubMedGoogle Scholar
  97. 97.
    Kishida K, Shimomura I, Kondo H, Kuriyama H, Makino Y, Nishizawa H, Maeda N, Matsuda M, Ouchi N, Kihara S, Kurachi Y, Funahashi T, Matsuzawa Y (2001) Genomic structure and insulin-mediated repression of the aquaporin adipose (AQPap), adipose-specific glycerol channel. J Biol Chem 276(39):36251–36260. doi: 10.1074/jbc.M106040200 PubMedGoogle Scholar
  98. 98.
    Kishida K, Shimomura I, Nishizawa H, Maeda N, Kuriyama H, Kondo H, Matsuda M, Nagaretani H, Ouchi N, Hotta K, Kihara S, Kadowaki T, Funahashi T, Matsuzawa Y (2001) Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor gamma. J Biol Chem 276(51):48572–48579. doi: 10.1074/jbc.M108213200 PubMedGoogle Scholar
  99. 99.
    Fasshauer M, Klein J, Lossner U, Klier M, Kralisch S, Paschke R (2003) Suppression of aquaporin adipose gene expression by isoproterenol, TNFalpha, and dexamethasone. Horm Metab Res 35(4):222–227. doi: 10.1055/s-2003-39478 PubMedGoogle Scholar
  100. 100.
    Rodriguez A, Gomez-Ambrosi J, Catalan V, Gil MJ, Becerril S, Sainz N, Silva C, Salvador J, Colina I, Fruhbeck G (2009) Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes (Lond) 33(5):541–552. doi: 10.1038/ijo.2009.40 Google Scholar
  101. 101.
    Sjoholm K, Palming J, Olofsson LE, Gummesson A, Svensson PA, Lystig TC, Jennische E, Brandberg J, Torgerson JS, Carlsson B, Carlsson LM (2005) A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A. J Clin Endocrinol Metab 90(4):2233–2239. doi: 10.1210/jc.2004-1830 PubMedGoogle Scholar
  102. 102.
    Maeda N, Funahashi T, Hibuse T, Nagasawa A, Kishida K, Kuriyama H, Nakamura T, Kihara S, Shimomura I, Matsuzawa Y (2004) Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue. Proc Natl Acad Sci USA 101(51):17801–17806PubMedCentralPubMedGoogle Scholar
  103. 103.
    Laforenza U, Scaffino MF, Gastaldi G (2013) Aquaporin-10 represents an alternative pathway for glycerol efflux from human adipocytes. PLoS One 8(1):e54474. doi: 10.1371/journal.pone.0054474 PubMedCentralPubMedGoogle Scholar
  104. 104.
    Serna A, Galan-Cobo A, Rodrigues C, Sanchez-Gomar I, Toledo-Aral JJ, Moura TF, Casini A, Soveral G, Echevarria M (2014) Functional inhibition of aquaporin-3 with a gold-based compound induces blockage of cell proliferation. J Cell Physiol 229(11):1787–1801. doi: 10.1002/jcp.24632 PubMedGoogle Scholar
  105. 105.
    Yasui H, Kubota M, Iguchi K, Usui S, Kiho T, Hirano K (2008) Membrane trafficking of aquaporin 3 induced by epinephrine. Biochem Biophys Res Commun 373(4):613–617. doi: 10.1016/j.bbrc.2008.06.086 PubMedGoogle Scholar
  106. 106.
    Gena P, Mastrodonato M, Portincasa P, Fanelli E, Mentino D, Rodriguez A, Marinelli RA, Brenner C, Fruhbeck G, Svelto M, Calamita G (2013) Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of non-alcoholic fatty liver disease. PLoS One 8(10):e78139. doi: 10.1371/journal.pone.0078139 PubMedCentralPubMedGoogle Scholar
  107. 107.
    Rodriguez A, Gena P, Mendez-Gimenez L, Rosito A, Valenti V, Rotellar F, Sola I, Moncada R, Silva C, Svelto M, Salvador J, Calamita G, Fruhbeck G (2014) Reduced hepatic aquaporin-9 and glycerol permeability are related to insulin resistance in non-alcoholic fatty liver disease. Int J Obes (Lond) 38(9):1213–1220. doi: 10.1038/ijo.2013.234 Google Scholar
  108. 108.
    Yeung CH, Cooper TG (2010) Aquaporin AQP11 in the testis: molecular identity and association with the processing of residual cytoplasm of elongated spermatids. Reproduction 139(1):209–216. doi: 10.1530/REP-09-0298 PubMedGoogle Scholar
  109. 109.
    Morishita Y, Matsuzaki T, Hara-chikuma M, Andoo A, Shimono M, Matsuki A, Kobayashi K, Ikeda M, Yamamoto T, Verkman A, Kusano E, Ookawara S, Takata K, Sasaki S, Ishibashi K (2005) Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule. Mol Cell Biol 25(17):7770–7779. doi: 10.1128/MCB.25.17.7770-7779.2005 PubMedCentralPubMedGoogle Scholar
  110. 110.
    Okada S, Misaka T, Tanaka Y, Matsumoto I, Ishibashi K, Sasaki S, Abe K (2008) Aquaporin-11 knockout mice and polycystic kidney disease animals share a common mechanism of cyst formation. FASEB J Off Publ Fed Am Soc Exp Biol 22(10):3672–3684Google Scholar
  111. 111.
    Rojek A, Fuchtbauer EM, Fuchtbauer A, Jelen S, Malmendal A, Fenton RA, Nielsen S (2013) Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding. Am J Physiol Gastrointest Liver Physiol 304(5):G501–G515. doi: 10.1152/ajpgi.00208.2012 PubMedGoogle Scholar
  112. 112.
    Madeira A, Fernandez-Veledo S, Camps M, Zorzano A, Moura TF, Ceperuelo-Mallafre V, Vendrell J, Soveral G (2014) Human aquaporin-11 is a water and glycerol channel and localizes in the vicinity of lipid droplets in human adipocytes. Obesity (Silver Spring). doi: 10.1002/oby.20792 Google Scholar
  113. 113.
    Gorelick DA, Praetorius J, Tsunenari T, Nielsen S, Agre P (2006) Aquaporin-11: a channel protein lacking apparent transport function expressed in brain. BMC Biochem 7:14. doi: 10.1186/1471-2091-7-14 PubMedCentralPubMedGoogle Scholar
  114. 114.
    Yakata K, Tani K, Fujiyoshi Y (2011) Water permeability and characterization of aquaporin-11. J Struct Biol 174(2):315–320. doi: 10.1016/j.jsb.2011.01.003 PubMedGoogle Scholar
  115. 115.
    Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445. doi: 10.1146/annurev-immunol-031210-101322 PubMedGoogle Scholar
  116. 116.
    Schroder K, Tschopp J (2010) The inflammasomes. Cell 140(6):821–832. doi: 10.1016/j.cell.2010.01.040 PubMedGoogle Scholar
  117. 117.
    Rabolli V, Wallemme L, Lo Re S, Uwambayinema F, Palmai-Pallag M, Thomassen L, Tyteca D, Octave JN, Marbaix E, Lison D, Devuyst O, Huaux F (2014) Critical role of aquaporins in interleukin 1beta (IL-1beta)-induced inflammation. J Biol Chem 289(20):13937–13947. doi: 10.1074/jbc.M113.534594 PubMedGoogle Scholar
  118. 118.
    Zhu N, Feng X, He C, Gao H, Yang L, Ma Q, Guo L, Qiao Y, Yang H, Ma T (2011) Defective macrophage function in aquaporin-3 deficiency. FASEB J 25(12):4233–4239. doi: 10.1096/fj.11-182808 PubMedGoogle Scholar

Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Ana Madeira
    • 1
    • 2
  • Teresa F. Moura
    • 1
    • 3
  • Graça Soveral
    • 1
    • 2
  1. 1.Research Institute for Medicines (iMed.ULisboa)Faculty of Pharmacy, Universidade de LisboaLisbonPortugal
  2. 2.Department of Bioquimica e Biologia Humana, Faculty of PharmacyUniversidade de LisboaLisbonPortugal
  3. 3.FCT-UNLCaparicaPortugal

Personalised recommendations