title: β3-adrenoceptor mediates metabolic protein remodeling in a rabbit model of tachypacing-induced atrial fibrillation.
abstract: BACKGROUND
  The beta 3-adrenoceptor (β3-AR) is closely associated with energy metabolism. This study aimed to explore the role of β3-AR in energy remodeling in a rabbit model of pacing-induced atrial fibrillation (AF).
  
  
  METHODS
  Rabbits with a sham-operation or pacing-induced AF were used for this study, and the latter group was further divided into three subgroups: 1) the pacing group, 2) the β3-AR agonist (BRL37344)-treated group, and 3) the β3-AR antagonist (SR59230A)-treated group. Atrial electrogram morphology and surface ECG were used to monitor the induction of AF and atrial effective refractory period (AERP). RT-PCR and western blot (WB) were used to show alterations in β3-AR and metabolic-related protein.
  
  
  RESULTS
  RT-PCR and WB results showed that β3-AR was significantly upregulated in the pacing group, and that it corresponded with high AF inducibility and significantly decreased AERP200 and ATP production in this group. Inhibition of β3-AR decreased the AF induction rate, reversed AERP200 reduction, and restored ATP levels in the AF rabbits. Further activation of β3-AR using agonist BRL37344 exacerbated AF-induced metabolic disruption. Periodic acid Schiff (PAS) and Oil Red O staining showed β3-AR-dependent glycogen and lipid droplet accumulation in cardiac myocytes with AF. Glucose transporter-4 (GLUT-4) and CD36, key transporters of glucose and fatty acids, were downregulated in the pacing group. Expression of carnitine-palmitoyltransferase I (CPT-1), a key regulator in fatty acid metabolism, was also significantly downregulated in the pacing group. Reduced glucose transportation and fatty acid oxidation could be restored by inhibition of β3-AR. Furthermore, key regulators of metabolism, peroxisome proliferator-activated receptor-α (PPARα) and PPAR co-activator (PGC-1α) can be regulated by pharmacological intervention of the β3-AR.
  
  
  CONCLUSIONS
  β3-AR is involved in metabolic protein remodeling in AF. PPARα/PGC-1α signaling pathway might be the relevant down-stream molecular machinery in response to AF-induced activation of β3-AR. β3-AR might be a novel target in AF treatment.
authors: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors: Yixi
authors: Y
authors: Liu
authors: Jianqiang
authors: J
authors: Geng
authors: Yutan
authors: Y
authors: Liu
authors: Yue
authors: Y
authors: Li
authors: Jingxia
authors: J
authors: Shen
authors: Xingping
authors: X
authors: Xiao
authors: Li
authors: L
authors: Sheng
authors: Baofeng
authors: B
authors: Yang
authors: Cheping
authors: C
authors: Cheng
authors: Weimin
authors: W
authors: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004562:Electrocardiography; D005227:Fatty Acids / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D022702:Receptors, Adrenergic, beta-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D018955:CD36 Antigens; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D047493:PPAR alpha; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D000255:Adenosine Triphosphate