title: Adipokines - removing road blocks to obesity and diabetes therapy.
abstract: Prevention of obesity and therapeutic weight loss interventions have provided only limited long term success. Therefore there is an urgent need to develop novel pharmacological treatment strategies, which target mechanisms underlying positive energy balance, excessive fat accumulation and adverse fat distribution. Adipokines may have potential for future pharmacological treatment strategies of obesity and metabolic diseases, because they are involved in the regulation of appetite and satiety, energy expenditure, endothelial function, blood pressure, insulin sensitivity, adipogenesis, fat distribution and insulin secretion and others. There are important road blocks on the way from an adipokine candidate to the clinical use a therapeutic compound. Such road blocks include an incomplete understanding of the mechanism of action, resistance to a specific adipokine, side effects of the adipokine and others. This review focuses on the potential of selected adipokines as therapeutic tools or targets and discusses important road blocks, which currently prevent their clinical use.
authors.affiliation: Department of Medicine, University of Leipzig, Liebigstr. 20, D-04103 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
keywords: Adipokines; Adiponectin; Apelin; BMP7; DPP4; Leptin; Nampt/visfatin; Nesfatin-1; Obesity; Road blocks; Therapeutic compounds; Type 2 diabetes; Vaspin
references.citation: Cell Metab. 2008 Nov;8(5):437-45
references.pmid: 19046574
references.citation: Obesity (Silver Spring). 2009 Sep;17(9):1736-43
references.pmid: 19521351
references.citation: Obes Rev. 2010 May;11(5):362-70
references.pmid: 19922430
references.citation: J Biol Chem. 1996 May 3;271(18):10697-703
references.pmid: 8631877
references.citation: Endocrinology. 2007 Apr;148(4):1539-49
references.pmid: 17204560
references.citation: J Clin Invest. 2002 May;109(10):1285-6
references.pmid: 12021242
references.citation: Exp Clin Endocrinol Diabetes. 2009 Jun;117(6):241-50
references.pmid: 19358089
references.citation: Drugs. 2013 Jun;73(9):989-97
references.pmid: 23740412
references.citation: Am J Physiol. 1997 Apr;272(4 Pt 1):E656-60
references.pmid: 9142888
references.citation: N Engl J Med. 2010 Sep 2;363(10):905-17
references.pmid: 20818901
references.citation: Dis Model Mech. 2012 Sep;5(5):621-6
references.pmid: 22915024
references.citation: Appl Physiol Nutr Metab. 2009 Jun;34(3):396-402
references.pmid: 19448705
references.citation: Diabetologia. 2011 Jul;54(7):1819-23
references.pmid: 21465327
references.citation: Diabetes. 2011 Jul;60(7):1917-25
references.pmid: 21593202
references.citation: J Endocrinol. 2011 Mar;208(3):R9-R16
references.pmid: 21224288
references.citation: Nature. 2006 Dec 14;444(7121):875-80
references.pmid: 17167476
references.citation: Nature. 2013 Nov 28;503(7477):493-9
references.pmid: 24172895
references.citation: J Clin Invest. 1997 Feb 1;99(3):385-90
references.pmid: 9022070
references.citation: J Pept Sci. 2012 Jun;18(6):383-93
references.pmid: 22565812
references.citation: PLoS One. 2012;7(10):e44270
references.pmid: 23049674
references.citation: Biochem Biophys Res Commun. 2002 Jan 25;290(3):1084-9
references.pmid: 11798186
references.citation: Exp Clin Endocrinol Diabetes. 2008 Sep;116 Suppl 1:S4-6
references.pmid: 18777452
references.citation: Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E199-206
references.pmid: 15271645
references.citation: J Clin Invest. 2002 Oct;110(8):1093-103
references.pmid: 12393845
references.citation: Science. 1995 Jul 28;269(5223):543-6
references.pmid: 7624777
references.citation: Life Sci. 2004 Feb 20;74(14):1801-16
references.pmid: 14741737
references.citation: Clin Pharmacol Ther. 2009 Dec;86(6):592-5
references.pmid: 19915603
references.citation: Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E506-15
references.pmid: 20570822
references.citation: Nature. 1997 Oct 9;389(6651):610-4
references.pmid: 9335502
references.citation: Int J Obes (Lond). 2005 Sep;29(9):1144-7
references.pmid: 15917841
references.citation: Am J Med. 2009 Jan;122(1 Suppl):S26-37
references.pmid: 19110085
references.citation: Endocrinology. 2008 Jun;149(6):2943-51
references.pmid: 18339717
references.citation: Nature. 2008 Aug 21;454(7207):1000-4
references.pmid: 18719589
references.citation: Obes Res. 2004 Apr;12(4):734-9
references.pmid: 15090644
references.citation: N Engl J Med. 1999 Sep 16;341(12):879-84
references.pmid: 10486419
references.citation: J Clin Endocrinol Metab. 2011 Jan;96(1):E146-50
references.pmid: 21047923
references.citation: Diabetologia. 2012 Sep;55(9):2319-26
references.pmid: 22688349
references.citation: Diabetes. 1994 Nov;43(11):1271-8
references.pmid: 7926300
references.citation: FASEB J. 2012 May;26(5):2187-96
references.pmid: 22331196
references.citation: Obes Facts. 2013;6(1):57-69
references.pmid: 23429279
references.citation: JAMA. 1999 Oct 27;282(16):1568-75
references.pmid: 10546697
references.citation: Metabolism. 2012 Dec;61(12):1659-65
references.pmid: 23021039
references.citation: Proteomics Clin Appl. 2012 Jan;6(1-2):91-101
references.pmid: 22213627
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10610-5
references.pmid: 16030142
references.citation: Expert Opin Pharmacother. 2009 Feb;10(2):239-54
references.pmid: 19236196
references.citation: Mol Cell Proteomics. 2012 Jan;11(1):M111.010504
references.pmid: 21947364
references.citation: Cell Mol Life Sci. 2013 Jul;70(14):2569-83
references.pmid: 23370777
references.citation: J Biol Chem. 2003 Jan 24;278(4):2461-8
references.pmid: 12431986
references.citation: Diabetes. 1996 Jul;45(7):881-5
references.pmid: 8666137
references.citation: J Clin Invest. 1995 May;95(5):2409-15
references.pmid: 7738205
references.citation: Cell Metab. 2013 Sep 3;18(3):333-40
references.pmid: 24011069
references.citation: Hepatology. 2008 Oct;48(4):1193-201
references.pmid: 18816630
references.citation: Diabetes Care. 2004 Jan;27(1):155-61
references.pmid: 14693982
references.citation: Biochem Biophys Res Commun. 2010 Jan 1;391(1):1039-42
references.pmid: 19995555
references.citation: Diabetes. 2005 Oct;54(10):2911-6
references.pmid: 16186392
references.citation: Arch Physiol Biochem. 2012 Jul;118(3):84-91
references.pmid: 22616691
references.citation: N Engl J Med. 2007 Aug 23;357(8):741-52
references.pmid: 17715408
references.citation: J Vasc Res. 2005 Nov-Dec;42(6):517-25
references.pmid: 16155368
references.citation: Diabetes. 2008 Feb;57(2):372-7
references.pmid: 17991760
references.citation: Science. 1993 Jan 1;259(5091):87-91
references.pmid: 7678183
references.citation: N Engl J Med. 2002 Feb 21;346(8):570-8
references.pmid: 11856796
references.citation: Endocr J. 2011;58(4):305-13
references.pmid: 21325742
references.citation: Cell Metab. 2007 Nov;6(5):363-75
references.pmid: 17983582
references.citation: Diabetes Care. 2012 Feb;35(2):342-9
references.pmid: 22190676
references.citation: J Clin Endocrinol Metab. 2000 Mar;85(3):1316-9
references.pmid: 10720082
references.citation: Am J Clin Nutr. 1987 Jan;45(1 Suppl):277-82
references.pmid: 3541569
references.citation: N Engl J Med. 2007 Apr 12;356(15):1517-26
references.pmid: 17429083
references.citation: J Biol Chem. 1995 Nov 10;270(45):26746-9
references.pmid: 7592907
references.citation: Int J Obes Relat Metab Disord. 1999 Feb;23 Suppl 1:37-41
references.pmid: 10193860
references.citation: Mol Med. 2011 Mar-Apr;17(3-4):189-93
references.pmid: 21103669
references.citation: Science. 1987 Jul 24;237(4813):405-8
references.pmid: 3299706
references.citation: Am J Med. 2011 Jan;124(1 Suppl):S3-18
references.pmid: 21194578
references.citation: Ann Intern Med. 1993 Oct 1;119(7 Pt 2):688-93
references.pmid: 8363198
references.citation: BMJ. 2013 Apr 09;346:f1515
references.pmid: 23571838
references.citation: Diabetes Metab J. 2012 Oct;36(5):317-27
references.pmid: 23130315
references.citation: Spine J. 2008 May-Jun;8(3):457-65
references.pmid: 17588821
references.citation: Hepatology. 2003 Feb;37(2):343-50
references.pmid: 12540784
references.citation: Endocrinology. 2011 Nov;152(11):4033-8
references.pmid: 21862618
references.citation: Nature. 1994 Dec 1;372(6505):425-32
references.pmid: 7984236
references.citation: Science. 2005 Jan 21;307(5708):426-30
references.pmid: 15604363
references.citation: Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1320-8
references.pmid: 23559624
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2005-10
references.pmid: 11172066
references.citation: Metabolism. 2012 Oct;61(10):1331-6
references.pmid: 22592129
references.citation: Proc Natl Acad Sci U S A. 2008 May 20;105(20):7257-62
references.pmid: 18458326
references.citation: Diabetes Care. 2013 Dec;36(12):4083-90
references.pmid: 24130353
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11178-83
references.pmid: 22711801
references.citation: Biochem Biophys Res Commun. 1996 Apr 16;221(2):286-9
references.pmid: 8619847
references.citation: Annu Rev Physiol. 2000;62:413-37
references.pmid: 10845097
references.citation: Eur J Clin Invest. 2004 Sep;34(9):641-2
references.pmid: 15379764
references.citation: Arch Intern Med. 2006 Apr 24;166(8):902-8
references.pmid: 16636217
references.citation: J Clin Endocrinol Metab. 2000 Nov;85(11):4003-9
references.pmid: 11095423
references.citation: Cell Metab. 2011 Oct 5;14(4):528-36
references.pmid: 21982712
references.citation: Open Med Chem J. 2011;5(Suppl 2):82-92
references.pmid: 21966329
references.citation: Diabetologia. 2008 May;51(5):827-35
references.pmid: 18369586
references.citation: Endocrine. 2011 Aug;40(1):1-9
references.pmid: 21725702
references.citation: Clin Pharmacol Ther. 2001 May;69(5):286-96
references.pmid: 11371996