title: Early impairment of skeletal muscle endothelial glycocalyx barrier properties in diet-induced obesity in mice.
abstract: While previous studies have indicated an important role for the endothelial glycocalyx in regulation of microvascular function, it was recently shown that acute enzymatic glycocalyx degradation in rats was associated with an impaired insulin-mediated glucose disposal. The aim of this study was to determine whether glycocalyx damage in skeletal muscle occurs at an early stage of diet-induced obesity (DIO). The microcirculation of the hindlimb muscle of anesthetized C57Bl/6 mice, fed chow (CON) or a high-fat diet (HFD) for 6 and 18 weeks (w), respectively, was visualized with a Sidestream Dark-Field camera, and glycocalyx barrier properties were derived from the calculated perfused boundary region (PBR). Subsequently, an intraperitoneal glucose tolerance test was performed and the area under the curve (AUC) of blood glucose was calculated. Impairment of glycocalyx barrier properties was already apparent after 6 weeks of HFD and remained after 18 weeks of HFD (PBR [in μm]: 0.81 ± 0.03 in CON_6w vs. 0.97 ± 0.04 in HFD_6w and 1.02 ± 0.07 in HFD_18w [both P < 0.05]). Glucose intolerance appeared to develop more slowly (AUC [in mmol/L × 120 min]: 989 ± 61 in CON_6w vs. 1204 ± 89 in HFD_6w [P = 0.11] and 1468 ± 84 in HFD_18w [P < 0.05]) than the impairment of glycocalyx barrier properties. The data indicate that damage to the endothelial glycocalyx is an early event in DIO. It is suggested that glycocalyx damage may contribute to the development of insulin resistance in obesity.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Bart J M
authors.initials: BJ
authors.lastname: Eskens
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Leurgans
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Vink
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Jurgen W G E
authors.initials: JW
authors.lastname: Vanteeffelen
keywords: Glycocalyx; Sidestream Dark‐Field imaging; high‐fat diet fed mouse model; insulin sensitivity
references.citation: Diabetes. 2004 Dec;53 Suppl 3:S215-9
references.pmid: 15561913
references.citation: Pflugers Arch. 2007 Jun;454(3):345-59
references.pmid: 17256154
references.citation: Br J Anaesth. 2012 Mar;108(3):384-94
references.pmid: 22290457
references.citation: J Intern Med. 2006 Apr;259(4):393-400
references.pmid: 16594907
references.citation: Diabetes. 2006 Feb;55(2):480-6
references.pmid: 16443784
references.citation: Pflugers Arch. 2009 Apr;457(6):1199-206
references.pmid: 18839207
references.citation: Hypertension. 2007 Jul;50(1):261-7
references.pmid: 17452501
references.citation: Thromb Haemost. 2011 May;105(5):790-801
references.pmid: 21174004
references.citation: Heart Vessels. 2010 May;25(3):254-62
references.pmid: 20512454
references.citation: Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E738-44
references.pmid: 12217891
references.citation: Circulation. 2006 Apr 18;113(15):1888-904
references.pmid: 16618833
references.citation: Circ Res. 2009 Jun 5;104(11):1318-25
references.pmid: 19443840
references.citation: Am J Physiol Heart Circ Physiol. 2009 May;296(5):H1451-6
references.pmid: 19286951
references.citation: J Appl Physiol (1985). 2013 May;114(9):1132-40
references.pmid: 23449940
references.citation: Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1323-32
references.pmid: 18812462
references.citation: Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H447-54
references.pmid: 15734874
references.citation: J Appl Physiol (1985). 2005 Oct;99(4):1471-6
references.pmid: 16024521
references.citation: Diabetes. 2002 Feb;51 Suppl 1:S109-16
references.pmid: 11815468
references.citation: Cardiovasc Res. 2004 Feb 15;61(3):620-9
references.pmid: 14962492
references.citation: Biorheology. 2009;46(3):181-9
references.pmid: 19581726
references.citation: Circ Res. 2003 Apr 4;92(6):592-4
references.pmid: 12637366
references.citation: Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E252-63
references.pmid: 21610226
references.citation: Trends Cardiovasc Med. 2007 Apr;17(3):101-5
references.pmid: 17418372
references.citation: Circ Res. 2005 Jun 10;96(11):1178-84
references.pmid: 15879311
references.citation: Diabetes. 2004 Jun;53(6):1418-23
references.pmid: 15161743
references.citation: Diabetes. 2013 Feb;62(2):343-5
references.pmid: 23349541
references.citation: Circ Res. 1996 Sep;79(3):581-9
references.pmid: 8781491
references.citation: Cerebrovasc Dis. 2013;35(5):451-4
references.pmid: 23735841
references.citation: Microcirculation. 2005 Jul-Aug;12(5):383-92
references.pmid: 16020387
references.citation: Microvasc Res. 2013 Nov;90:86-9
references.pmid: 23988876
references.citation: Am J Physiol. 1999 Aug;277(2):H508-14
references.pmid: 10444475
references.citation: J Lipid Res. 2011 Sep;52(9):1712-22
references.pmid: 21700834
references.citation: Microvasc Res. 2011 Nov;82(3):416-22
references.pmid: 21889944
references.citation: QJM. 2008 Jul;101(7):513-8
references.pmid: 18319293
references.citation: PLoS One. 2013;8(1):e55399
references.pmid: 23383178
references.citation: Int J Cardiol. 2013 Oct 12;168(5):5026-8
references.pmid: 23968713
references.citation: Pflugers Arch. 2000 Sep;440(5):653-66
references.pmid: 11007304
references.citation: Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1541-7
references.pmid: 12855481
references.citation: Clin Sci (Lond). 2005 Aug;109(2):143-59
references.pmid: 16033329
references.citation: Diabetes Care. 2007 Mar;30(3):753-9
references.pmid: 17327355
references.citation: Nutr Metab (Lond). 2010 Mar 27;7:24
references.pmid: 20346174
references.citation: J Appl Physiol (1985). 2008 Mar;104(3):845-52
references.pmid: 18162484
references.citation: Am J Physiol. 1994 Aug;267(2 Pt 1):E187-202
references.pmid: 8074198
references.citation: Circulation. 2004 Jun 1;109(21):2529-35
references.pmid: 15136505
references.citation: J Appl Toxicol. 2001 Jan-Feb;21(1):15-23
references.pmid: 11180276
references.citation: J Pharmacol Exp Ther. 2009 Jan;328(1):123-30
references.pmid: 18941121
references.citation: J Intern Med. 2006 Apr;259(4):339-50
references.pmid: 16594902
references.citation: Diabetes. 2002 Feb;51 Suppl 1:S212-20
references.pmid: 11815482
references.citation: J Am Soc Nephrol. 2012 Nov;23(11):1900-8
references.pmid: 23085635
references.citation: Am J Pathol. 2013 May;182(5):1532-40
references.pmid: 23518410
references.citation: Opt Express. 2007 Nov 12;15(23):15101-14
references.pmid: 19550794
references.citation: Diabetes Obes Metab. 2010 Sep;12(9):798-805
references.pmid: 20649632
references.citation: Diabetologia. 2010 Dec;53(12):2646-55
references.pmid: 20865240
references.citation: Circulation. 2000 Apr 4;101(13):1500-2
references.pmid: 10747340
references.citation: Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E732-50
references.pmid: 18612041