title: The renin angiotensin system and the metabolic syndrome.
abstract: The renin angiotensin system (RAS; most well-known for its critical roles in the regulation of cardiovascular function and hydromineral balance) has regained the spotlight for its potential roles in various aspects of the metabolic syndrome. It may serve as a causal link among obesity and several co-morbidities. Drugs that reduce the synthesis or action of angiotensin-II (A-II; the primary effector peptide of the RAS) have been used to treat hypertension for decades and, more recently, clinical trials have determined the utility of these pharmacological agents to prevent insulin resistance. Moreover, there is evidence that the RAS contributes to body weight regulation by acting in various tissues. This review summarizes what is known of the actions of the RAS in the brain and throughout the body to influence various metabolic disorders. Special emphasis is given to the role of the RAS in body weight regulation. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
authors.affiliation: Program in Neuroscience University of Cincinnati, Cincinnati, OH 45237, United States. dekloead@mail.uc.edu
authors.forename: Annette D
authors.initials: AD
authors.lastname: de Kloet
authors.forename: Eric G
authors.initials: EG
authors.lastname: Krause
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D007328:Insulin
references.citation: Behav Neurosci. 1988 Dec;102(6):953-60
references.pmid: 2850816
references.citation: Neurosci Lett. 1982 Apr 16;29(2):123-7
references.pmid: 6283434
references.citation: J Intern Med. 2008 Apr;263(4):336-52
references.pmid: 18312311
references.citation: Biochem Biophys Res Commun. 2002 Jun 7;294(2):441-7
references.pmid: 12051731
references.citation: J Physiol. 2007 Oct 15;584(Pt 2):613-23
references.pmid: 17702818
references.citation: FEBS Lett. 2001 Apr 27;495(3):197-200
references.pmid: 11334891
references.citation: Physiol Behav. 2009 Aug 4;98(1-2):192-7
references.pmid: 19465040
references.citation: Antioxid Redox Signal. 2007 Jul;9(7):869-78
references.pmid: 17508912
references.citation: J Clin Invest. 2002 Jun;109(11):1417-27
references.pmid: 12045255
references.citation: Am J Physiol. 1982 Jan;242(1):R136-40
references.pmid: 7036759
references.citation: J Pharmacol Exp Ther. 1998 Aug;286(2):718-26
references.pmid: 9694926
references.citation: J Hypertens. 1998 May;16(5):571-5
references.pmid: 9797167
references.citation: Exp Physiol. 2008 May;93(5):665-75
references.pmid: 18263657
references.citation: J Endocrinol. 1999 May;161(2):317-22
references.pmid: 10320830
references.citation: J Pharmacol Exp Ther. 2005 Jun;313(3):1035-45
references.pmid: 15681656
references.citation: Am J Physiol Endocrinol Metab. 2005 Jun;288(6):E1074-81
references.pmid: 15657091
references.citation: Diabetes. 2004 Apr;53(4):989-97
references.pmid: 15047614
references.citation: J Hepatol. 2009 Jun;50(6):1226-35
references.pmid: 19395110
references.citation: Am J Hypertens. 2007 May;20(5):579-86
references.pmid: 17485025
references.citation: Brain Res. 1982 Aug 12;245(2):317-25
references.pmid: 6289966
references.citation: J Biol Chem. 2005 Aug 26;280(34):30113-9
references.pmid: 15983030
references.citation: Am J Physiol. 1993 Dec;265(6 Pt 1):E860-5
references.pmid: 8279541
references.citation: J Mol Med (Berl). 2001 Apr;79(2-3):71-3
references.pmid: 11357940
references.citation: Pharmacol Ther. 2010 Jan;125(1):27-38
references.pmid: 19723538
references.citation: FASEB J. 2001 Dec;15(14):2727-9
references.pmid: 11606482
references.citation: Diabetologia. 1998 Feb;41(2):127-33
references.pmid: 9498644
references.citation: Science. 2001 Dec 7;294(5549):2166-70
references.pmid: 11739957
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R781-8
references.pmid: 18650320
references.citation: Am J Physiol. 1994 Mar;266(3 Pt 1):E453-8
references.pmid: 8166267
references.citation: Curr Opin Nephrol Hypertens. 2004 May;13(3):325-32
references.pmid: 15073492
references.citation: Metabolism. 2006 Apr;55(4):478-88
references.pmid: 16546478
references.citation: Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E227-32
references.pmid: 15082419
references.citation: Science. 1971 Jul 2;173(3991):64-5
references.pmid: 4325865
references.citation: Brain Res. 1997 May 23;757(2):218-27
references.pmid: 9200750
references.citation: J Clin Invest. 1996 Aug 1;98(3):671-9
references.pmid: 8698858
references.citation: Eur J Pharmacol. 2006 Dec 15;552(1-3):112-22
references.pmid: 17064684
references.citation: Diabetes Care. 2005 Sep;28(9):2261-6
references.pmid: 16123505
references.citation: Endocrinology. 2007 Nov;148(11):5442-50
references.pmid: 17690163
references.citation: J Neural Transm Gen Sect. 1994;98(2):159-64
references.pmid: 7734113
references.citation: Cell Metab. 2007 Dec;6(6):506-12
references.pmid: 18054319
references.citation: N Engl J Med. 1991 Apr 18;324(16):1098-104
references.pmid: 1759997
references.citation: Hypertension. 1990 Jun;15(6 Pt 2):867-71
references.pmid: 2351437
references.citation: Histochemistry. 1988;89(4):323-31
references.pmid: 3410745
references.citation: Front Neuroendocrinol. 1997 Oct;18(4):383-439
references.pmid: 9344632
references.citation: Biochem Biophys Res Commun. 2002 Jan 25;290(3):1084-9
references.pmid: 11798186
references.citation: Am J Physiol. 1993 Jun;264(6 Pt 1):C1570-6
references.pmid: 8333506
references.citation: Lancet. 2007 Apr 7;369(9568):1208-19
references.pmid: 17416265
references.citation: Gastroenterology. 2002 Nov;123(5):1667-76
references.pmid: 12404241
references.citation: Clin Exp Pharmacol Physiol. 2005 Apr;32(4):302-7
references.pmid: 15810996
references.citation: Am J Physiol. 1998 May;274(5):E867-76
references.pmid: 9612245
references.citation: J Neural Transm Suppl. 1991;34:129-37
references.pmid: 1667868
references.citation: Physiol Behav. 2008 Mar 18;93(4-5):820-5
references.pmid: 18191966
references.citation: Diabetologia. 2009 May;52(5):752-64
references.pmid: 19283361
references.citation: Diabetes Metab. 2004 Dec;30(6):487-96
references.pmid: 15671918
references.citation: Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E891-5
references.pmid: 14749209
references.citation: Science. 1998 May 29;280(5368):1378-83
references.pmid: 9603721
references.citation: Diabetes Obes Metab. 2003 Nov;5(6):462-7
references.pmid: 14617233
references.citation: Endocrinology. 1997 Apr;138(4):1512-9
references.pmid: 9075710
references.citation: J Hypertens. 2005 Oct;23(10):1777-81
references.pmid: 16148594
references.citation: Circ Res. 1995 Jan;76(1):1-15
references.pmid: 8001266
references.citation: J Hypertens. 2004 Mar;22(3):645-52
references.pmid: 15076172
references.citation: Exp Physiol. 2009 Jan;94(1):130-7
references.pmid: 18723579
references.citation: Endocrinology. 1994 Nov;135(5):2030-6
references.pmid: 7956925
references.citation: Curr Opin Pharmacol. 2008 Apr;8(2):127-32
references.pmid: 18243793
references.citation: Nat Rev Neurosci. 2003 Nov;4(11):901-9
references.pmid: 14595401
references.citation: J Clin Invest. 1997 Nov 1;100(9):2158-69
references.pmid: 9410892
references.citation: Biochem Biophys Res Commun. 1998 Sep 8;250(1):77-82
references.pmid: 9735335
references.citation: JAMA. 2006 Apr 5;295(13):1549-55
references.pmid: 16595758
references.citation: Trends Pharmacol Sci. 2009 May;30(5):234-9
references.pmid: 19359049
references.citation: J Am Coll Cardiol. 2005 Sep 6;46(5):821-6
references.pmid: 16139131
references.citation: Adv Exp Med Biol. 1996;396:39-47
references.pmid: 8726684
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8258-63
references.pmid: 12829792
references.citation: Biochem Biophys Res Commun. 2006 Jun 16;344(4):1224-33
references.pmid: 16650382
references.citation: Endocrinology. 1987 Nov;121(5):1616-26
references.pmid: 3665835
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6531-6
references.pmid: 18443281
references.citation: Biochem J. 1997 Feb 15;322 ( Pt 1):235-9
references.pmid: 9078267
references.citation: Am J Physiol. 1993 Aug;265(2 Pt 2):R302-9
references.pmid: 8103642
references.citation: Diabetes. 2008 Feb;57(2):340-7
references.pmid: 18025412
references.citation: Nature. 2000 Apr 6;404(6778):661-71
references.pmid: 10766253
references.citation: Diabetes. 2005 Apr;54(4):991-9
references.pmid: 15793237
references.citation: J Hypertens. 2004 Oct;22(10):1977-82
references.pmid: 15361770
references.citation: Biochem Biophys Res Commun. 2005 Jul 15;332(4):927-33
references.pmid: 15922295
references.citation: Circ Res. 2000 Sep 1;87(5):E1-9
references.pmid: 10969042
references.citation: J Neural Transm (Vienna). 1999;106(7-8):631-44
references.pmid: 10907723
references.citation: Diabetes. 2006 Feb;55(2):367-74
references.pmid: 16443769
references.citation: Am J Physiol. 1997 Mar;272(3 Pt 1):C989-99
references.pmid: 9124535
references.citation: Regul Pept. 1995 May 4;57(1):1-18
references.pmid: 7644700
references.citation: J Clin Invest. 2003 Jul;112(1):83-90
references.pmid: 12840062
references.citation: J Neurosci. 1999 May 15;19(10):3952-61
references.pmid: 10234025
references.citation: Regul Pept. 2004 Jul 15;119(3):213-9
references.pmid: 15120483
references.citation: Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E345-51
references.pmid: 18073321
references.citation: Endocrinology. 1999 Jan;140(1):154-8
references.pmid: 9886820
references.citation: N Engl J Med. 2000 Mar 30;342(13):905-12
references.pmid: 10738048
references.citation: Peptides. 2005 Jul;26(7):1270-7
references.pmid: 15949646
references.citation: Neuroendocrinology. 1995 Apr;61(4):437-44
references.pmid: 7783857
references.citation: Endocrinology. 2001 Jan;142(1):487-92
references.pmid: 11145613
references.citation: Int Immunopharmacol. 2008 Feb;8(2):312-8
references.pmid: 18182246
references.citation: Hypertension. 2005 Mar;45(3):356-62
references.pmid: 15630041
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Sep;281(3):R795-802
references.pmid: 11506994
references.citation: Hypertension. 2002 Nov;40(5):609-11
references.pmid: 12411451
references.citation: Lancet. 2003 Mar 29;361(9363):1077-83
references.pmid: 12672310
references.citation: Appetite. 2007 Sep;49(2):353-67
references.pmid: 17561308
references.citation: Endocrinology. 2004 Jan;145(1):169-74
references.pmid: 14512436
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Apr;280(4):R1095-104
references.pmid: 11247832
references.citation: Hypertension. 2004 May;43(5):1003-10
references.pmid: 15037562
references.citation: Mol Cancer Ther. 2003 Nov;2(11):1139-47
references.pmid: 14617787
references.citation: Obes Res. 2005 Nov;13(11):1909-14
references.pmid: 16339122
references.citation: JOP. 2001 Jan;2(1):26-32
references.pmid: 11862019
references.citation: J Neurosci. 2003 Jun 15;23(12):5041-9
references.pmid: 12832527
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2):R422-8
references.pmid: 15117728
references.citation: J Endocrinol. 1999 Jan;160(1):13-9
references.pmid: 9854172
references.citation: Am J Physiol. 1997 Jul;273(1 Pt 2):R236-42
references.pmid: 9249555
references.citation: Hypertension. 1988 Jun;11(6 Pt 2):591-6
references.pmid: 2839415
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12490-5
references.pmid: 8901609
references.citation: Biochem J. 2001 Aug 1;357(Pt 3):899-904
references.pmid: 11463364
references.citation: Diabetes Metab. 2004 Dec;30(6):498-505
references.pmid: 15671919
references.citation: Endocrinology. 2009 Sep;150(9):4114-23
references.pmid: 19497971
references.citation: Cancer Lett. 2006 Jan 18;231(2):290-4
references.pmid: 16399230
references.citation: Trends Endocrinol Metab. 2005 Sep;16(7):293-9
references.pmid: 16061390
references.citation: J Biol Chem. 2000 Oct 27;275(43):33238-43
references.pmid: 10924499
references.citation: Horm Metab Res. 2000 Nov-Dec;32(11-12):500-3
references.pmid: 11246815
references.citation: Hypertension. 1992 Apr;19(4):339-44
references.pmid: 1555865
references.citation: Am J Physiol Endocrinol Metab. 2004 Nov;287(5):E955-61
references.pmid: 15213064
references.citation: Br J Cancer. 2005 Aug 22;93(4):425-34
references.pmid: 16052213
references.citation: Diabetologia. 2004 Feb;47(2):240-8
references.pmid: 14722647
references.citation: Am J Physiol Cell Physiol. 2009 Sep;297(3):C601-10
references.pmid: 19535516
references.citation: Cardiovasc Diabetol. 2007 Nov 27;6:36
references.pmid: 18042288
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Oct;287(4):R943-9
references.pmid: 15191907
references.citation: Compr Ther. 1989 Nov;15(11):51-8
references.pmid: 2684484
references.citation: Int Immunopharmacol. 2008 Feb;8(2):247-53
references.pmid: 18182235
references.citation: J Hypertens. 2006 Aug;24(8):1607-17
references.pmid: 16877964
references.citation: N Engl J Med. 1981 Apr 16;304(16):930-3
references.pmid: 7010165
references.citation: Endocrinology. 1993 Aug;133(2):939-41
references.pmid: 8344227
references.citation: J Hypertens. 2006 Sep;24(9):1809-16
references.pmid: 16915030
references.citation: Circulation. 2005 Apr 12;111(14):1806-13
references.pmid: 15809376
references.citation: Exp Physiol. 2008 May;93(5):519-27
references.pmid: 18310257
references.citation: Am J Hypertens. 2007 Apr;20(4):431-6
references.pmid: 17386352
references.citation: Diabetes. 2002 Jun;51(6):1699-707
references.pmid: 12031955
references.citation: Eur J Pharmacol. 2008 Jan 28;579(1-3):426-32
references.pmid: 18078928
references.citation: Physiol Genomics. 2005 Nov 17;23(3):311-7
references.pmid: 16131528
references.citation: Endocrinology. 2001 Dec;142(12):5220-5
references.pmid: 11713218
references.citation: Physiol Rev. 2006 Jul;86(3):747-803
references.pmid: 16816138
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10730-5
references.pmid: 12149466
references.citation: J Clin Invest. 2002 Mar;109(5):603-11
references.pmid: 11877468
references.citation: Endocrinology. 2009 Mar;150(3):1421-8
references.pmid: 18948399
references.citation: Neuroendocrinology. 2000 Nov;72(5):306-17
references.pmid: 11124587
references.citation: Circulation. 2004 May 4;109(17):2054-7
references.pmid: 15117841
references.citation: J Hypertens. 2005 Aug;23(8):1525-30
references.pmid: 16003179
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2548-56
references.pmid: 15181022
references.citation: Endocrinology. 1991 May;128(5):2248-52
references.pmid: 1850346
references.citation: Diabetologia. 1991 Feb;34(2):119-25
references.pmid: 2065846
references.citation: Nat Med. 2004 Jun;10(6):625-32
references.pmid: 15133506
references.citation: J Mol Endocrinol. 2001 Jun;26(3):155-64
references.pmid: 11432370
references.citation: Endocrinology. 2005 Aug;146(8):3481-9
references.pmid: 15878965
references.citation: Endocrinology. 2008 Dec;149(12):6416-24
references.pmid: 18687780