PMID- 23228666
OWN - NLM
STAT- MEDLINE
DCOM- 20130625
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 430
IP  - 2
DP  - 2013 Jan 11
TI  - Induction of mitochondrial biogenesis and respiration is associated with mTOR 
      regulation in hepatocytes of rats treated with the pan-PPAR activator 
      tetradecylthioacetic acid (TTA).
PG  - 573-8
LID - S0006-291X(12)02311-X [pii]
LID - 10.1016/j.bbrc.2012.11.111 [doi]
AB  - The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) 
      activators has been explained by increasing mitochondrial fatty acid oxidation, 
      as observed in livers of rats treated with the pan-PPAR activator 
      tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain 
      the metabolic adaptations observed in hepatocytes after treatment with TTA. We 
      therefore characterized the mitochondrial effects, and linked this to signalling 
      by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes 
      isolated from TTA-treated rats, the changes in cellular content and morphology 
      were consistent with hypertrophy. This was associated with induction of multiple 
      mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs 
      of mitochondrial proteins. Transcription analysis further confirmed activation of 
      PPARalpha-associated genes, in addition to genes related to mitochondrial biogenesis 
      and function. Analysis of mitochondrial respiration revealed that the capacity of 
      both electron transport and oxidative phosphorylation were increased. These 
      effects coincided with activation of the stress related factor, ERK1/2, and mTOR. 
      The protein level and phosphorylation of the downstream mTOR actors eIF4G and 
      4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by 
      inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via 
      adaptive regulation of PPARs as well as mTOR.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Hagland, Hanne R
AU  - Hagland HR
AD  - Department of Biomedicine, University of Bergen, Norway.
FAU - Nilsson, Linn I H
AU  - Nilsson LI
FAU - Burri, Lena
AU  - Burri L
FAU - Nikolaisen, Julie
AU  - Nikolaisen J
FAU - Berge, Rolf K
AU  - Berge RK
FAU - Tronstad, Karl J
AU  - Tronstad KJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121207
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Sulfides)
RN  - 7ZU5I25S2O (1-(carboxymethylthio)tetradecane)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Enlargement
MH  - Cells, Cultured
MH  - Hepatocytes/*drug effects/enzymology/ultrastructure
MH  - Hypolipidemic Agents/*pharmacology
MH  - Male
MH  - Mitochondria, Liver/*drug effects/enzymology
MH  - Mitochondrial Turnover/*drug effects
MH  - Oxidation-Reduction
MH  - Oxidative Phosphorylation/drug effects
MH  - Oxygen Consumption/*drug effects
MH  - Peroxisome Proliferator-Activated Receptors/*agonists
MH  - Rats
MH  - Rats, Wistar
MH  - Sulfides/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2012/12/12 06:00
MHDA- 2013/06/26 06:00
CRDT- 2012/12/12 06:00
PHST- 2012/11/23 00:00 [received]
PHST- 2012/11/27 00:00 [accepted]
PHST- 2012/12/12 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
AID - S0006-291X(12)02311-X [pii]
AID - 10.1016/j.bbrc.2012.11.111 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Jan 11;430(2):573-8. doi: 
      10.1016/j.bbrc.2012.11.111. Epub 2012 Dec 7.