PMID- 23624629
OWN - NLM
STAT- MEDLINE
DCOM- 20130912
LR  - 20211203
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 305
IP  - 1
DP  - 2013 Jul 1
TI  - Regulation of fatty acid metabolism by mTOR in adult murine hearts occurs 
      independently of changes in PGC-1alpha.
PG  - H41-51
LID - 10.1152/ajpheart.00877.2012 [doi]
AB  - Mechanistic target of rapamycin (mTOR) is essential for cardiac development, 
      growth, and function, but the role of mTOR in the regulation of cardiac 
      metabolism and mitochondrial respiration is not well established. This study 
      sought to determine cardiac metabolism and mitochondrial bioenergetics in mice 
      with inducible deletion of mTOR in the adult heart. Doxycycline-inducible and 
      cardiac-specific mTOR-deficient mice were generated by crossing cardiac-specific 
      doxycycline-inducible tetO-Cre mice with mice harboring mTOR floxed alleles. 
      Deletion of mTOR reduced mTORC1 and mTORC2 signaling after in vivo insulin 
      stimulation. Maximum and minimum dP/dt measured by cardiac catheterization in 
      vivo under anesthesia and cardiac output, cardiac power, and aortic pressure in 
      ex vivo working hearts were unchanged, suggesting preserved cardiac function 4 wk 
      after doxycycline treatment. However, myocardial palmitate oxidation was 
      impaired, whereas glucose oxidation was increased. Consistent with reduced 
      palmitate oxidation, expression of fatty acid metabolism genes fatty acid-binding 
      protein 3, medium-chain acyl-CoA dehydrogenase, and hydroxyacyl-CoA 
      dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional 
      protein)-alpha and -beta was reduced, and carnitine palmitoyl transferase-1 and -2 
      enzymatic activity was decreased. Mitochondrial palmitoyl carnitine respiration 
      was diminished. However, mRNA for peroxisome proliferator-activated receptor-gamma 
      coactivator (PGC)-1alpha and -1beta, protein levels of PGC-1alpha, and electron transport 
      chain subunits, mitochondrial DNA, and morphology were unchanged. Also, 
      pyruvate-supported and FCCP-stimulated respirations were unchanged, suggesting 
      that mTOR deletion induces a specific defect in fatty acid utilization. In 
      conclusion, mTOR regulates mitochondrial fatty acid utilization but not glucose 
      utilization in the heart via mechanisms that are independent of changes in PGC 
      expression.
FAU - Zhu, Yi
AU  - Zhu Y
AD  - Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School 
      of Medicine, Salt Lake City, UT 84112, USA.
FAU - Soto, Jamie
AU  - Soto J
FAU - Anderson, Brandon
AU  - Anderson B
FAU - Riehle, Christian
AU  - Riehle C
FAU - Zhang, Yi Cheng
AU  - Zhang YC
FAU - Wende, Adam R
AU  - Wende AR
FAU - Jones, Deborah
AU  - Jones D
FAU - McClain, Donald A
AU  - McClain DA
FAU - Abel, E Dale
AU  - Abel ED
LA  - eng
GR  - I01 BX001140/BX/BLRD VA/United States
GR  - U54 HL112311/HL/NHLBI NIH HHS/United States
GR  - R01 HL108379/HL/NHLBI NIH HHS/United States
GR  - R01-DK-092065/DK/NIDDK NIH HHS/United States
GR  - R01-HL-108379/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130426
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Fatty Acids)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Blood Pressure
MH  - Cardiac Output
MH  - DNA, Mitochondrial/metabolism
MH  - Fatty Acids/genetics/*metabolism
MH  - Heart/physiology
MH  - Metabolome
MH  - Mice
MH  - Mitochondria, Heart/*metabolism
MH  - Myocardium/*metabolism
MH  - Oxidation-Reduction
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors
MH  - Transcription, Genetic
PMC - PMC3727103
OTO - NOTNLM
OT  - cardiac substrate metabolism
OT  - mechanistic target of rapamycin
OT  - mitochondrial respiration
OT  - peroxisome proliferator-activated receptor-gamma coactivator-1alpha
EDAT- 2013/04/30 06:00
MHDA- 2013/09/13 06:00
PMCR- 2014/07/01
CRDT- 2013/04/30 06:00
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2013/09/13 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - ajpheart.00877.2012 [pii]
AID - H-00877-2012 [pii]
AID - 10.1152/ajpheart.00877.2012 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2013 Jul 1;305(1):H41-51. doi: 
      10.1152/ajpheart.00877.2012. Epub 2013 Apr 26.