title: Adiponectin resistance and vascular dysfunction in the hyperlipidemic state.
abstract: Insulin plays an important role in the stimulation of vascular nitric oxide production, with both short term (vasomotility and anti-thrombotic effects) and long term (smooth muscle cell growth and migration inhibition) benefits. Impaired vasodilatory response to insulin, the hallmark of vascular insulin resistance (IR), has important implications for circulatory pathophysiology. An association between adipokines and IR has been observed in both diabetic and nondiabetic states. Adiponectin (APN) is an insulin-sensitizing adipokine known to stimulate skeletal muscle fatty acid (FA) oxidation and reduce lipid accumulation. Recent demonstrations of potential cross-talk between APN and insulin in vascular function regulation are particularly interesting. The lipid accumulation observed after chronic high-fat (HF) diets and in the obese state may reduce vascular response to APN, a pathologic state termed as APN resistance. This review highlights the importance of insulin sensitivity and APN activity in the maintenance of endothelial function. It explores the relationships between vascular IR and APN resistance in the hyperlipidemic pathological condition, representative of the metabolic syndrome. The investigation of vascular insulin and APN resistance provides not only better understanding of vascular pathophysiology, but also an opportunity for therapeutic targeting in individuals affected by the metabolic syndrome.
authors.affiliation: Department of Geriatrics, Xijing Hospital, Xi-an, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Xin Liang
authors.initials: XL
authors.lastname: Ma
mesh_terms: D052242:Adiponectin / Q000502:physiology*; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction; D014652:Vascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D014655:Vascular Resistance
chemical_list: D052242:Adiponectin; D005227:Fatty Acids; D007328:Insulin; D009569:Nitric Oxide
references.citation: Am J Obstet Gynecol. 1990 Aug;163(2):505-8
references.pmid: 2386136
references.citation: J Biol Chem. 2002 Feb 1;277(5):3286-92
references.pmid: 11723139
references.citation: Free Radic Biol Med. 1998 Sep;25(4-5):385-91
references.pmid: 9741577
references.citation: Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E298-305
references.pmid: 16507604
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14367-72
references.pmid: 9826706
references.citation: Biochem Biophys Res Commun. 2004 Mar 5;315(2):264-71
references.pmid: 14766203
references.citation: Diabetes. 1999 Jun;48(6):1323-30
references.pmid: 10342823
references.citation: J Clin Invest. 1989 May;83(5):1774-7
references.pmid: 2540223
references.citation: Am J Physiol Endocrinol Metab. 2003 Jan;284(1):E1-6
references.pmid: 12388172
references.citation: J Clin Invest. 1996 Jun 1;97(11):2601-10
references.pmid: 8647954
references.citation: Circulation. 2002 Jun 18;105(24):2893-8
references.pmid: 12070119
references.citation: Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2255-7
references.pmid: 18802013
references.citation: Biochem J. 2000 Feb 1;345 Pt 3:673-80
references.pmid: 10642527
references.citation: J Lipid Res. 2007 Feb;48(2):444-52
references.pmid: 17050906
references.citation: J Appl Physiol (1985). 2006 May;100(5):1467-74
references.pmid: 16357064
references.citation: Nature. 2000 Apr 13;404(6779):787-90
references.pmid: 10783895
references.citation: Diabetes. 2000 Jun;49(6):896-903
references.pmid: 10866040
references.citation: Am J Physiol. 1994 Jun;266(6 Pt 2):H2568-72
references.pmid: 8024019
references.citation: Diabetologia. 1994 Feb;37(2):214-6
references.pmid: 8163058
references.citation: Diabetes. 2005 Jul;54(7):2003-11
references.pmid: 15983200
references.citation: Circulation. 2002 Nov 26;106(22):2767-70
references.pmid: 12451000
references.citation: Diabetes. 1997 Sep;46 Suppl 2:S9-13
references.pmid: 9285492
references.citation: J Biol Chem. 2002 Jan 18;277(3):1794-9
references.pmid: 11707433
references.citation: J Mol Cell Cardiol. 2009 Mar;46(3):413-9
references.pmid: 19027750
references.citation: J Clin Endocrinol Metab. 2004 Feb;89(2):765-9
references.pmid: 14764794
references.citation: Am J Physiol Endocrinol Metab. 2005 May;288(5):E876-82
references.pmid: 15613685
references.citation: J Biol Chem. 2002 Oct 4;277(40):37487-91
references.pmid: 12138120
references.citation: Biol Chem Hoppe Seyler. 1994 Feb;375(2):81-8
references.pmid: 8192861
references.citation: EMBO J. 1998 Jun 1;17(11):3045-51
references.pmid: 9606187
references.citation: Obesity (Silver Spring). 2006 Nov;14(11):1898-904
references.pmid: 17135604
references.citation: J Biol Chem. 2004 Jul 16;279(29):30817-22
references.pmid: 15123605
references.citation: Biochem Biophys Res Commun. 2004 Aug 13;321(1):154-60
references.pmid: 15358228
references.citation: J Biol Chem. 2003 Jan 24;278(4):2461-8
references.pmid: 12431986
references.citation: J Clin Endocrinol Metab. 1997 Dec;82(12):4117-21
references.pmid: 9398724
references.citation: J Biol Chem. 2004 Jun 11;279(24):25211-8
references.pmid: 15069082
references.citation: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E83-90
references.pmid: 17356008
references.citation: Br J Pharmacol. 2008 Oct;155(3):326-34
references.pmid: 18574454
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Feb;296(2):R243-51
references.pmid: 19073900
references.citation: Diabetes Care. 2002 Jun;25(6):1055-9
references.pmid: 12032114
references.citation: Diabetes. 2006 Sep;55(9):2562-70
references.pmid: 16936205
references.citation: J Clin Invest. 2001 Nov;108(9):1341-8
references.pmid: 11696579
references.citation: Circ Res. 2001 Jun 22;88(12):1276-82
references.pmid: 11420304
references.citation: Diabetes. 2004 Sep;53(9):2195-201
references.pmid: 15331527
references.citation: J Biol Chem. 2003 Oct 10;278(41):40352-63
references.pmid: 12878598
references.citation: J Biol Chem. 2001 Aug 10;276(32):30392-8
references.pmid: 11402048
references.citation: J Immunol. 2000 Jul 1;165(1):102-7
references.pmid: 10861041
references.citation: J Clin Invest. 1997 Sep 1;100(5):1230-9
references.pmid: 9276741
references.citation: Diabetes. 1998 Apr;47(4):660-7
references.pmid: 9568701
references.citation: J Biol Chem. 2002 Feb 22;277(8):6214-22
references.pmid: 11739394
references.citation: Endocrinology. 2002 Mar;143(3):998-1007
references.pmid: 11861525
references.citation: Diabetes. 2006 Feb;55(2):480-6
references.pmid: 16443784
references.citation: Hypertension. 2003 Sep;42(3):231-4
references.pmid: 12860835
references.citation: Circ Res. 1993 Feb;72(2):403-12
references.pmid: 8418991
references.citation: FASEB J. 2003 Aug;17(11):1511-3
references.pmid: 12824289
references.citation: Nat Med. 2001 Aug;7(8):947-53
references.pmid: 11479628
references.citation: J Lipid Res. 1996 Aug;37(8):1802-11
references.pmid: 8864964
references.citation: J Biol Chem. 2004 Jan 9;279(2):1304-9
references.pmid: 14557259
references.citation: Nat Med. 2002 Nov;8(11):1288-95
references.pmid: 12368907
references.citation: Tissue Eng. 2000 Jun;6(3):241-51
references.pmid: 10941219
references.citation: Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1595-9
references.pmid: 10845877
references.citation: J Biol Chem. 2003 Nov 7;278(45):45021-6
references.pmid: 12944390
references.citation: Eur J Clin Invest. 2002 May;32(5):328-34
references.pmid: 12027872
references.citation: J Clin Invest. 2001 Dec;108(12):1875-81
references.pmid: 11748271
references.citation: Diabetes. 2004 Nov;53(11):2873-82
references.pmid: 15504968
references.citation: Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):27-32
references.pmid: 18988893
references.citation: Circulation. 1997 Aug 19;96(4):1282-90
references.pmid: 9286960
references.citation: Diabetes. 2005 Nov;54(11):3154-60
references.pmid: 16249439
references.citation: Nat Med. 2001 Aug;7(8):941-6
references.pmid: 11479627
references.citation: Diabetes. 2002 Apr;51(4):1138-45
references.pmid: 11916937
references.citation: Diabetes Care. 2004 Mar;27(3):739-45
references.pmid: 14988295
references.citation: Diabetes. 2007 Aug;56(8):1969-76
references.pmid: 17475934
references.citation: Diabetes. 2000 Dec;49(12):2178-89
references.pmid: 11118023
references.citation: J Clin Invest. 1990 Jun;85(6):1844-52
references.pmid: 2189893
references.citation: Diabetologia. 2005 Jan;48(1):132-9
references.pmid: 15619075
references.citation: Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):224-30
references.pmid: 16269667
references.citation: Am J Physiol Endocrinol Metab. 2001 Feb;280(2):E229-37
references.pmid: 11158925
references.citation: Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1703-8
references.pmid: 17895290
references.citation: Nat Med. 2002 Jul;8(7):731-7
references.pmid: 12068289
references.citation: BMC Pharmacol. 2004 Oct 18;4:23
references.pmid: 15491498
references.citation: Circulation. 2000 Sep 12;102(11):1296-301
references.pmid: 10982546
references.citation: Hepatology. 2007 Jul;46(1):130-9
references.pmid: 17526025
references.citation: Biochem Pharmacol. 2005 Mar 1;69(5):781-90
references.pmid: 15710355
references.citation: Circulation. 2008 Aug 12;118(7):731-42
references.pmid: 18663085
references.citation: J Clin Invest. 1999 Aug;104(4):447-57
references.pmid: 10449437
references.citation: Diabetes. 2002 Apr;51(4):1118-24
references.pmid: 11916934
references.citation: Br J Obstet Gynaecol. 1997 Feb;104(2):229-34
references.pmid: 9070145
references.citation: Diabetes. 2006 Jun;55(6):1840-6
references.pmid: 16731851