title: Protection against cardiac hypertrophy by geniposide involves the GLP-1 receptor / AMPKα signalling pathway.
abstract: OBJECTIVE
  Activation of glucagon-like peptide-1 (GLP-1) receptor exerts a range of cardioprotective effects. Geniposide is an agonist of GLP-1 receptor, but its role in cardiac hypertrophy remains completely unknown. Here, we have investigated its protective effects and clarified the underlying molecular mechanisms.
  
  
  METHODS
  The transverse aorta was constricted in C57/B6 mice and then geniposide was given orally for 7 weeks. Morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers were used to evaluate hypertrophy.
  
  
  RESULTS
  Geniposide inhibited the hypertrophic response induced by constriction of the transverse aorta or by isoprenaline. Activation of 5'-AMP-activated protein kinase-α (AMPKα) and inhibition of mammalian target of rapamycin, ERK and endoplasmic reticulum stress were observed in hypertrophic hearts that were treated with geniposide. Furthermore, Compound C (CpC) or knock-down of AMPKα restricted protection of geniposide against cell hypertrophy and activation of mammalian target of rapamycin and ERK induced by hypertrophic stimuli. CpC or shAMPKα also abolished the protection of geniposide against endoplasmic reticulum stress induced by thapsigargin or dihtiothreitol. The cardio-protective effects of geniposide were ablated in mice subjected to CpC. GLP-1receptor blockade counteracted the anti-hypertrophic response and activation of AMPKα by geniposide. Knock-down of GLP-1 receptor also offset the inhibitory effects of geniposide on cardiac hypertrophy in vivo.
  
  
  CONCLUSIONS
  Geniposide protected against cardiac hypertrophy via activation of the GLP-1 receptor/AMPKα pathway. Geniposide is a potential therapeutic drug for cardiac hypertrophy.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Zhen-Guo
authors: ZG
authors: Ma
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Jia
authors: J
authors: Dai
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Wen-Bin
authors: WB
authors: Zhang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Yuan
authors: Y
authors: Yuan
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Hai-Han
authors: HH
authors: Liao
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Ning
authors: N
authors: Zhang
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Zhou-Yan
authors: ZY
authors: Bian
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Qi-Zhu
authors: QZ
authors: Tang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D039823:Iridoids; C007835:geniposide; D052216:Glucagon-Like Peptide 1; D055372:AMP-Activated Protein Kinases