title: Aquaporin-10 represents an alternative pathway for glycerol efflux from human adipocytes.
abstract: BACKGROUND
  Glycerol outflow from adipocytes has been considered for a decade to be mediated by aquaporin-7, an aquaglyceroporin highly expressed in the adipose tissue. Its involvement in glycerol metabolism has been widely studied also in humans. Recent studies in different aquaporin-7 KO mice models pose two different questions 1) the exact localization of aquaporin-7 in human white adipose tissue; 2) the existence of other aquaglyceroporins that work with aquaporin-7 to guarantee glycerol efflux and thus a normal adiposity in humans. To this purpose we investigated the expression, the localization and the functioning of aquaglyceroporin-10 in subcutaneous white adipose tissue, in isolated and cultured differentiated adipocytes.
  
  
  RESULTS
  Aquaporin-7 and -10 were expressed in the white adipose tissue both at mRNA and at protein level. Immunofluorescence revealed aquaporin-7 and -10 labelling in the human adipose tissue both to the plasma membrane and to a thin rim of cytoplasm of adipocytes. Aquaporin-7, but not aquaporin-10, colocalized with the endothelial marker CD34. Human cultured differentiated adipocytes showed an aquaporin-7 and -10 labelling mainly in the cytoplasm and in the lipid droplets with insulin reinforcing the lipid droplets staining and isoproterenol inducing its translocation to the plasma membrane compartment. Water and glycerol permeability measurements using adipocytes and adipose membrane vesicles confirmed the presence of functioning aquaglyceroporins. Aquaporin-10 silencing in human differentiated adipocytes resulted in a 50% decrease of glycerol and osmotic water permeability.
  
  
  CONCLUSIONS
  The results indicate that aquaporin-7, differently from mice, is present in both adipocyte and capillary plasma membranes of human adipose tissue. Aquaporin-10, on the contrary, is expressed exclusively in the adipocytes. The expression of two aquaglyceroporins in human adipose tissue is particularly important for the maintenance of normal or low glycerol contents inside the adipocyte, thus protecting humans from obesity.
authors: Department of Molecular Medicine, University of Pavia, Pavia, Italy. lumberto@unipv.it
authors: Umberto
authors: U
authors: Laforenza
authors: Manuela F
authors: MF
authors: Scaffino
authors: Giulia
authors: G
authors: Gastaldi
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000368:Aged; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C438667:AQP10 protein, human; C114141:AQP7 protein, human; D020346:Aquaporins; D007328:Insulin; D012333:RNA, Messenger; D007545:Isoproterenol; D005990:Glycerol
references: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10993-8
references: 16009937
references: J Biol Chem. 1988 Sep 15;263(26):13432-9
references: 3047124
references: Biol Cell. 2005 Nov;97(11):823-9
references: 15898950
references: J Histochem Cytochem. 2003 Jun;51(6):773-80
references: 12754288
references: J Membr Biol. 2000 Jan 15;173(2):73-87
references: 10630923
references: Trends Pharmacol Sci. 2006 Jul;27(7):345-7
references: 16764946
references: Anal Biochem. 2009 Jun 1;389(1):89-91
references: 19303392
references: Am J Physiol Renal Physiol. 2007 Mar;292(3):F956-65
references: 17077387
references: J Nutr. 2005 Oct;135(10):2329-36
references: 16177191
references: Diabetes. 2007 May;56(5):1468-74
references: 17351148
references: Biochem Biophys Res Commun. 2001 Oct 5;287(4):814-9
references: 11573934
references: J Biol Chem. 2005 Apr 22;280(16):15493-6
references: 15746100
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Int J Obes (Lond). 2007 Jul;31(7):1165-71
references: 17245390
references: Biochim Biophys Acta. 2002 Jul 19;1576(3):335-40
references: 12084581
references: Annu Rev Physiol. 2008;70:301-27
references: 17961083
references: Cell. 1994 Nov 4;79(3):427-36
references: 7954810
references: J Biol Chem. 1964 Feb;239:375-80
references: 14169133
references: J Biol Chem. 1993 Oct 25;268(30):22756-64
references: 8226786
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Biol Cell. 2005 Aug;97(8):605-13
references: 15943587
references: Nature. 2005 Nov 24;438(7067):436-7
references: 16306977
references: Biochem Biophys Res Commun. 2002 Jun 14;294(3):630-4
references: 12056815
references: Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17801-6
references: 15591341
references: J Physiol. 2002 Jul 1;542(Pt 1):3-16
references: 12096044
references: Mol Cell Biol. 2007 Sep;27(17):6026-37
references: 17576812
references: J Biomed Mater Res A. 2010 Sep 1;94(3):790-9
references: 20336739
references: Biochem Biophys Res Commun. 1997 Dec 8;241(1):53-8
references: 9405233
references: J Biol Chem. 2006 Jun 16;281(24):16202-6
references: 16624821
references: Histochem Cell Biol. 2004 Jun;121(6):463-71
references: 15221416
references: Mol Aspects Med. 2012 Oct-Dec;33(5-6):642-50
references: 22465691
references: J Biol Chem. 2001 Dec 21;276(51):48572-9
references: 11679588
references: J Membr Biol. 1989 Sep;110(2):147-62
references: 2553975
references: J Biol Chem. 2000 Jul 7;275(27):20896-902
references: 10777495
references: Horm Metab Res. 2003 Apr;35(4):222-7
references: 12778365
references: Cell Mol Biol (Noisy-le-grand). 2006 Oct 30;52(7):20-7
references: 17543217
references: J Clin Endocrinol Metab. 2007 Sep;92(9):3640-5
references: 17566090
references: Eur J Biochem. 2002 Apr;269(7):1814-26
references: 11952783
references: J Clin Endocrinol Metab. 2011 Apr;96(4):E586-97
references: 21289260
references: Biochem Biophys Res Commun. 2006 Jan 20;339(3):785-9
references: 16325777
references: Biol Cell. 2010 May 26;102(8):457-67
references: 20415666
references: Biochem Cell Biol. 2007 Dec;85(6):675-84
references: 18059526