title: Adiponectin suppresses gluconeogenic gene expression in mouse hepatocytes independent of LKB1-AMPK signaling.
abstract: The adipocyte-derived hormone adiponectin signals from the fat storage depot to regulate metabolism in peripheral tissues. Inversely correlated with body fat levels, adiponectin reduction in obese individuals may play a causal role in the symptoms of metabolic syndrome. Adiponectin lowers serum glucose through suppression of hepatic glucose production, an effect attributed to activation of AMPK. Here, we investigated the signaling pathways that mediate the effects of adiponectin by studying mice with inducible hepatic deletion of LKB1, an upstream regulator of AMPK. We found that loss of LKB1 in the liver partially impaired the ability of adiponectin to lower serum glucose, though other actions of the hormone were preserved, including reduction of gluconeogenic gene expression and hepatic glucose production as assessed by euglycemic hyperinsulinemic clamp. Furthermore, in primary mouse hepatocytes, the absence of LKB1, AMPK, or the transcriptional coactivator CRTC2 did not prevent adiponectin from inhibiting glucose output or reducing gluconeogenic gene expression. These results reveal that whereas some of the hormone's actions in vivo may be LKB1 dependent, substantial LKB1-, AMPK-, and CRTC2-independent signaling pathways also mediate effects of adiponectin.
authors: The Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Russell A
authors: RA
authors: Miller
authors: Qingwei
authors: Q
authors: Chu
authors: John
authors: J
authors: Le Lay
authors: Philipp E
authors: PE
authors: Scherer
authors: Rexford S
authors: RS
authors: Ahima
authors: Klaus H
authors: KH
authors: Kaestner
authors: Marc
authors: M
authors: Foretz
authors: Benoit
authors: B
authors: Viollet
authors: Morris J
authors: MJ
authors: Birnbaum
references: Methods Cell Biol. 1976;13:29-83
references: 177845
references: EMBO J. 2005 May 18;24(10):1810-20
references: 15889149
references: Nat Med. 2004 May;10(5):524-9
references: 15077108
references: Nat Med. 2001 Aug;7(8):941-6
references: 11479627
references: Diabetologia. 2005 Jan;48(1):132-9
references: 15619075
references: J Biol Chem. 2005 Aug 12;280(32):29060-6
references: 15980064
references: J Clin Invest. 2003 Jan;111(1):91-8
references: 12511592
references: Science. 2005 Dec 9;310(5754):1642-6
references: 16308421
references: J Biol Chem. 2009 Aug 14;284(33):22426-22435
references: 19520843
references: J Clin Invest. 2010 Jul;120(7):2355-69
references: 20577053
references: Diabetes Res Clin Pract. 2006 Aug;73(2):135-42
references: 16503364
references: Nature. 2008 Nov 13;456(7219):269-73
references: 18849969
references: Nat Med. 2007 Mar;13(3):332-9
references: 17268472
references: Nature. 2003 Jun 12;423(6941):762-9
references: 12802337
references: Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E211-24
references: 19435851
references: Nature. 2002 Sep 12;419(6903):162-7
references: 12226664
references: Cell Metab. 2009 Jul;10(1):55-62
references: 19583954
references: Cell Metab. 2007 Jul;6(1):55-68
references: 17618856
references: PLoS One. 2010 Jun 21;5(6):e11239
references: 20574539
references: J Am Coll Cardiol. 2004 Apr 7;43(7):1195-200
references: 15063429
references: Nat Cell Biol. 2006 May;8(5):516-23
references: 16622416
references: Diabetes. 2006 Sep;55(9):2562-70
references: 16936205
references: J Biol Chem. 2006 Feb 3;281(5):2654-60
references: 16326714
references: J Clin Invest. 2010 Jul;120(7):2267-70
references: 20577046
references: Bioessays. 2001 Dec;23(12):1112-9
references: 11746230
references: Oncogene. 2008 Apr 7;27(16):2320-36
references: 18391974
references: J Clin Invest. 2007 Sep;117(9):2621-37
references: 17717599
references: J Biol Chem. 1995 Nov 10;270(45):26746-9
references: 7592907
references: J Biol Chem. 2002 May 31;277(22):19521-9
references: 11912203
references: Nature. 2005 Oct 20;437(7062):1109-11
references: 16148943
references: Acta Physiol (Oxf). 2009 May;196(1):81-98
references: 19245656
references: Nat Med. 2011 Jan;17(1):55-63
references: 21186369
references: Eur J Biochem. 1989 Dec 8;186(1-2):129-36
references: 2598924
references: J Biol. 2003;2(4):28
references: 14511394
references: Diabetes. 2006 Nov;55(11):3083-90
references: 17065346
references: Mol Cell Biol. 2006 Nov;26(22):8217-27
references: 16966378
references: Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):85-9
references: 12524229
references: Nat Med. 2001 Aug;7(8):947-53
references: 11479628
references: Nat Med. 2002 Nov;8(11):1288-95
references: 12368907
references: Biochem Biophys Res Commun. 2009 Apr 24;382(1):51-6
references: 19254698
references: Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1595-9
references: 10845877
references: Curr Biol. 2003 Nov 11;13(22):2004-8
references: 14614828
references: J Cell Biochem. 2008 Aug 1;104(5):1724-39
references: 18348280
references: J Clin Invest. 2001 Dec;108(12):1875-81
references: 11748271
references: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2005-10
references: 11172066
references: Am J Physiol Gastrointest Liver Physiol. 2009 Sep;297(3):G611-8
references: 19608729
references: J Clin Invest. 2003 Jul;112(1):91-100
references: 12840063
references: J Biol Chem. 1996 May 3;271(18):10697-703
references: 8631877
references: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3329-35
references: 14985505