PMID- 27199111
OWN - NLM
STAT- MEDLINE
DCOM- 20170706
LR  - 20211204
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 311
IP  - 1
DP  - 2016 Jul 1
TI  - Discordant signaling and autophagy response to fasting in hearts of obese mice: 
      Implications for ischemia tolerance.
PG  - H219-28
LID - 10.1152/ajpheart.00041.2016 [doi]
AB  - Autophagy is regulated by nutrient and energy status and plays an adaptive role 
      during nutrient deprivation and ischemic stress. Metabolic syndrome (MetS) is a 
      hypernutritive state characterized by obesity, dyslipidemia, elevated fasting 
      blood glucose levels, and insulin resistance. It has also been associated with 
      impaired autophagic flux and larger-sized infarcts. We hypothesized that 
      diet-induced obesity (DIO) affects nutrient sensing, explaining the observed 
      cardiac impaired autophagy. We subjected male friend virus B NIH (FVBN) mice to a 
      high-fat diet, which resulted in increased weight gain, fat deposition, 
      hyperglycemia, insulin resistance, and larger infarcts after myocardial 
      ischemia-reperfusion. Autophagic flux was impaired after 4 wk on a high-fat diet. 
      To interrogate nutrient-sensing pathways, DIO mice were subjected to overnight 
      fasting, and hearts were processed for biochemical and proteomic analysis. Obese 
      mice failed to upregulate LC3-II or to clear p62/SQSTM1 after fasting, although 
      mRNA for LC3B and p62/SQSTM1 were appropriately upregulated in both groups, 
      demonstrating an intact transcriptional response to fasting. Energy- and 
      nutrient-sensing signal transduction pathways [AMPK and mammalian target of 
      rapamycin (mTOR)] also responded appropriately to fasting, although mTOR was more 
      profoundly suppressed in obese mice. Proteomic quantitative analysis of the 
      hearts under fed and fasted conditions revealed broad changes in protein networks 
      involved in oxidative phosphorylation, autophagy, oxidative stress, protein 
      homeostasis, and contractile machinery. In many instances, the fasting response 
      was quite discordant between lean and DIO mice. Network analysis implicated the 
      peroxisome proliferator-activated receptor and mTOR regulatory nodes. Hearts of 
      obese mice exhibited impaired autophagy, altered proteome, and discordant 
      response to nutrient deprivation.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Andres, Allen M
AU  - Andres AM
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and Allen.Andres@cshs.org.
FAU - Kooren, Joel A
AU  - Kooren JA
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Parker, Sarah J
AU  - Parker SJ
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Tucker, Kyle C
AU  - Tucker KC
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Ravindran, Nandini
AU  - Ravindran N
AD  - Donald P. Shiley BioScience Center, San Diego State University, San Diego, 
      California.
FAU - Ito, Bruce R
AU  - Ito BR
AD  - Donald P. Shiley BioScience Center, San Diego State University, San Diego, 
      California.
FAU - Huang, Chengqun
AU  - Huang C
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Venkatraman, Vidya
AU  - Venkatraman V
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Van Eyk, Jennifer E
AU  - Van Eyk JE
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Gottlieb, Roberta A
AU  - Gottlieb RA
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
FAU - Mentzer, Robert M Jr
AU  - Mentzer RM Jr
AD  - Cedars-Sinai Heart Institute and Department of Medicine, Los Angeles, California; 
      Barbra Streisand Women's Heart Center of Cedars-Sinai Medical Center, Los 
      Angeles, California; and.
LA  - eng
GR  - P01 HL112730/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20160506
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Sequestosome-1 Protein)
RN  - 0 (Sqstm1 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - *Autophagy
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Energy Metabolism
MH  - Fasting/*metabolism
MH  - Male
MH  - Metabolic Syndrome/etiology/metabolism
MH  - Mice
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Myocardial Infarction/etiology/*metabolism/physiopathology
MH  - Myocardial Reperfusion Injury/etiology/*metabolism/pathology
MH  - Myocardium/*metabolism/pathology
MH  - Obesity/complications/*metabolism/pathology
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - Protein Interaction Maps
MH  - Proteolysis
MH  - Proteomics/methods
MH  - Sequestosome-1 Protein/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Time Factors
PMC - PMC4967197
OTO - NOTNLM
OT  - mammalian target of rapamycin
OT  - metabolic syndrome
OT  - peroxisome proliferator-activated receptor-alpha/gamma
OT  - proteomics
EDAT- 2016/05/21 06:00
MHDA- 2017/07/07 06:00
PMCR- 2017/07/01
CRDT- 2016/05/21 06:00
PHST- 2016/01/15 00:00 [received]
PHST- 2016/05/03 00:00 [accepted]
PHST- 2016/05/21 06:00 [entrez]
PHST- 2016/05/21 06:00 [pubmed]
PHST- 2017/07/07 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - ajpheart.00041.2016 [pii]
AID - H-00041-2016 [pii]
AID - 10.1152/ajpheart.00041.2016 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H219-28. doi: 
      10.1152/ajpheart.00041.2016. Epub 2016 May 6.