PMID- 23886954
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20220310
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 438
IP  - 1
DP  - 2013 Aug 16
TI  - Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes.
PG  - 211-7
LID - S0006-291X(13)01206-0 [pii]
LID - 10.1016/j.bbrc.2013.07.055 [doi]
AB  - Nebivolol is a third-generation beta-adrenergic receptor (beta-AR) blocker with 
      additional beneficial effects, including the improvement of lipid and glucose 
      metabolism in obese individuals. However, the underlying mechanism of nebivolol's 
      role in regulating the lipid profile remains largely unknown. In this study, we 
      investigated the role of nebivolol in mitochondrial biogenesis in 3T3-L1 
      adipocytes. Exposure of 3T3-L1 cells to nebivolol for 24h increased mitochondrial 
      DNA copy number, mitochondrial protein levels and the expression of transcription 
      factors involved in mitochondrial biogenesis, including PPAR-gamma coactivator-1alpha 
      (PGC-1alpha), Sirtuin 3 (Sirt3), mitochondrial transcription factor A (Tfam) and 
      nuclear related factor 1 (Nrf1). These changes were accompanied by an increase in 
      oxygen consumption and in the expression of genes involved in fatty acid 
      oxidation and antioxidant enzymes in 3T3-L1 adipocytes, including 
      nebivolol-induced endothelial nitric oxide synthase (eNOS), as well as an 
      increase in the formation of cyclic guanosine monophosphate (cGMP). Pretreatment 
      with NG-nitro-L-arginine methyl ester (L-NAME) attenuated nebivolol-induced 
      mitochondrial biogenesis, as did the soluble guanylate cyclase inhibitor, ODQ. 
      Treatment with nebivolol and beta3-AR blocker SR59230A markedly attenuated PGC-1alpha, 
      Sirt3 and manganese superoxide dismutase (MnSOD) protein levels in comparison to 
      treatment with nebivolol alone. These data indicate that the mitochondrial 
      synthesis and metabolism in adipocytes that is promoted by nebivolol is primarily 
      mediated through the eNOS/cGMP-dependent pathway and is initiated by the 
      activation of beta3-AR receptors.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Huang, Chenglin
AU  - Huang C
AD  - State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular 
      Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, 
      Shanghai Jiaotong University, Shanghai 200025, PR China.
FAU - Chen, Dongrui
AU  - Chen D
FAU - Xie, Qihai
AU  - Xie Q
FAU - Yang, Ying
AU  - Yang Y
FAU - Shen, Weili
AU  - Shen W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130722
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adrenergic beta-3 Receptor Antagonists)
RN  - 0 (Benzopyrans)
RN  - 0 (Ethanolamines)
RN  - 0 (Receptors, Adrenergic, beta-3)
RN  - 030Y90569U (Nebivolol)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects/*metabolism/ultrastructure
MH  - Adrenergic beta-3 Receptor Antagonists/*pharmacology
MH  - Animals
MH  - Benzopyrans/*pharmacology
MH  - Ethanolamines/*pharmacology
MH  - Mice
MH  - Mitochondria/*drug effects/*metabolism
MH  - Nebivolol
MH  - Receptors, Adrenergic, beta-3/*metabolism
OTO - NOTNLM
OT  - Adipocyte
OT  - Mitochondrial biogenesis
OT  - Nebivolol
EDAT- 2013/07/28 06:00
MHDA- 2013/11/05 06:00
CRDT- 2013/07/27 06:00
PHST- 2013/07/10 00:00 [received]
PHST- 2013/07/15 00:00 [accepted]
PHST- 2013/07/27 06:00 [entrez]
PHST- 2013/07/28 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
AID - S0006-291X(13)01206-0 [pii]
AID - 10.1016/j.bbrc.2013.07.055 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Aug 16;438(1):211-7. doi: 
      10.1016/j.bbrc.2013.07.055. Epub 2013 Jul 22.