Document Detail


C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.
MedLine Citation:
PMID:  22828478     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained compensated function could provide useful information for developing metabolic therapies to treat heart failure. The molecular signaling for this metabolic change may occur through O-GlcNAcylation. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
Authors:
Aaron K Olson; Dolena Ledee; Kate Iwamoto; Masaki Kajimoto; Colleen O'Kelly Priddy; Nancy Isern; Michael A Portman
Related Documents :
1148508 - Characterization of an inhibitory receptor in rat hippocampus: a microiontophoretic stu...
2139298 - Extracellular levels of quinolinic acid are moderately increased in rat neostriatum fol...
1664338 - Comparison of (1s,3r)-1-aminocyclopentane-1,3-dicarboxylic acid (1s,3r-acpd)- and 1r,3s...
9641558 - Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynur...
7902638 - Effects of halothane on the synthesis of neurotransmitter amino acids in mouse brain.
16833458 - Density changes accompanying wave propagation in the cerium-catalyzed belousov-zhabotin...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-07-22
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  55     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-07-03     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  156-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetyl Coenzyme A / metabolism
Animals
Cardiomegaly / genetics*,  metabolism*,  ultrasonography
Citric Acid Cycle*
Disease Models, Animal
Echocardiography
Fatty Acids, Nonesterified / metabolism*
Male
Mice
Mice, Transgenic
Oxidation-Reduction
Oxygen Consumption
Proteome
Proto-Oncogene Proteins c-myc / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
K08 HL092333/HL/NHLBI NIH HHS; K08-HL-092333/HL/NHLBI NIH HHS; T32 HL007828/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Proteome; 0/Proto-Oncogene Proteins c-myc; 72-89-9/Acetyl Coenzyme A
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  TASTE LOSS IN THE ELDERLY: EPIDEMIOLOGY, CAUSES AND CONSEQUENCES.
Next Document:  Electronic properties and charge transfer phenomena in Pt nanoparticles on ?-Al2O3: size, shape, sup...