title: Liver X receptor agonist treatment attenuates cardiac dysfunction in type 2 diabetic db/db mice.
abstract: BACKGROUND
  Liver X receptor (LXR) plays a critical regulatory role in metabolism and inflammation, and has been demonstrated to be involved in cardiovascular physiology/pathology. In the present study, we investigated the effect of GW3965, a potent LXR agonist, on diabetic cardiomyopathy (DCM) in type 2 diabetic db/db mice.
  
  
  RESULTS
  Non-diabetic db/+ mice and diabetic db/db mice received either vehicle or LXR agonist GW3965 for 12 weeks. Systemic insulin resistance was evaluated by glucose tolerance test and homeostasis model assessment for insulin resistance. Endpoint cardiac function was assessed by echocardiography and catheterization. Ventricular tissue was collected for histology and gene/protein expression analysis. Untreated db/db diabetic mice exhibited diastolic dysfunction with adverse structural remodeling (including myocardial fibrosis and increased apoptosis). Treatment with GW3965 remarkably attenuated myocardial dysfunction and structural remodeling in diabetic db/db mice. Mechanistically, GW3965 restored Akt phosphorylation and inhibited MAP kinases phosphorylation, and reduced oxidative/nitrative stress and inflammation response in the diabetic myocardium.
  
  
  CONCLUSIONS
  Our data demonstrate that GW3965 exerts a cardioprotective effect against DCM by (at least in part) attenuating insulin resistance, modulating Akt and MAP kinases pathways, and reducing oxidative/nitrative stress and inflammatory response. These findings strongly suggest that LXR agonist may have therapeutic potential in treating DCM.
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. dr.heqing@gmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. pujun310@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. yuanac@yahoo.com.cn.
authors.forename: Ancai
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. ytbnh@126.com.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. akoma78@hotmail.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. franky.superior@gmail.com.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. xulongwei1234321@163.com.
authors.forename: Longwei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. travelh@163.com.
authors.forename: Huan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. heben1026@hotmail.com.
authors.forename: Ben
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy*; D006321:Heart / Q000187:drug effects*; D007333:Insulin Resistance / Q000502:physiology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D001565:Benzoates; D001596:Benzylamines; C473027:GW 3965; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors