PMID- 25888508
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20211203
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 308
IP  - 12
DP  - 2015 Jun 15
TI  - Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart 
      after ischemia-reperfusion.
PG  - H1530-9
LID - 10.1152/ajpheart.00008.2015 [doi]
AB  - Diet-induced obesity deteriorates the recovery of cardiac function after 
      ischemia-reperfusion (I/R) injury. While mechanistic target of rapamycin (mTOR) 
      is a key mediator of energy metabolism, the effects of cardiac mTOR in ischemic 
      injury under metabolic syndrome remains undefined. Using cardiac-specific 
      transgenic mice overexpressing mTOR (mTOR-Tg mice), we studied the effect of mTOR 
      on cardiac function in both ex vivo and in vivo models of I/R injury in high-fat 
      diet (HFD)-induced obese mice. mTOR-Tg and wild-type (WT) mice were fed a HFD 
      (60% fat by calories) for 12 wk. Glucose intolerance and insulin resistance 
      induced by the HFD were comparable between WT HFD-fed and mTOR-Tg HFD-fed mice. 
      Functional recovery after I/R in the ex vivo Langendorff perfusion model was 
      significantly lower in HFD-fed mice than normal chow diet-fed mice. mTOR-Tg mice 
      demonstrated better cardiac function recovery and had less of the necrotic 
      markers creatine kinase and lactate dehydrogenase in both feeding conditions. 
      Additionally, mTOR overexpression suppressed expression of proinflammatory 
      cytokines, including IL-6 and TNF-alpha, in both feeding conditions after I/R injury. 
      In vivo I/R models showed that at 1 wk after I/R, HFD-fed mice exhibited worse 
      cardiac function and larger myocardial scarring along myofibers compared with 
      normal chow diet-fed mice. In both feeding conditions, mTOR overexpression 
      preserved cardiac function and prevented myocardial scarring. These findings 
      suggest that cardiac mTOR overexpression is sufficient to prevent the detrimental 
      effects of diet-induced obesity on the heart after I/R, by reducing cardiac 
      dysfunction and myocardial scarring.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Aoyagi, Toshinori
AU  - Aoyagi T
AD  - Department of Anatomy, Biochemistry and Physiology, Center for Cardiovascular 
      Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 
      Hawaii.
FAU - Higa, Jason K
AU  - Higa JK
AD  - Department of Anatomy, Biochemistry and Physiology, Center for Cardiovascular 
      Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 
      Hawaii.
FAU - Aoyagi, Hiroko
AU  - Aoyagi H
AD  - Department of Anatomy, Biochemistry and Physiology, Center for Cardiovascular 
      Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 
      Hawaii.
FAU - Yorichika, Naaiko
AU  - Yorichika N
AD  - Department of Anatomy, Biochemistry and Physiology, Center for Cardiovascular 
      Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 
      Hawaii.
FAU - Shimada, Briana K
AU  - Shimada BK
AD  - Department of Anatomy, Biochemistry and Physiology, Center for Cardiovascular 
      Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 
      Hawaii.
FAU - Matsui, Takashi
AU  - Matsui T
AD  - Department of Anatomy, Biochemistry and Physiology, Center for Cardiovascular 
      Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, 
      Hawaii tmatsui@hawaii.edu.
LA  - eng
GR  - R01-HL-098423/HL/NHLBI NIH HHS/United States
GR  - T32-HL-115505/HL/NHLBI NIH HHS/United States
GR  - R01 HL098423/HL/NHLBI NIH HHS/United States
GR  - T32 HL115505/HL/NHLBI NIH HHS/United States
GR  - G12-MD-007601/MD/NIMHD NIH HHS/United States
GR  - P30 GM103341/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150417
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Inflammation Mediators)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Diet, High-Fat
MH  - Disease Models, Animal
MH  - Glucose Intolerance/enzymology/etiology
MH  - Inflammation Mediators/metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Mice, Transgenic
MH  - Myocardial Contraction
MH  - Myocardial Infarction/enzymology/etiology/genetics/pathology/physiopathology
MH  - Myocardial Reperfusion 
      Injury/enzymology/etiology/genetics/pathology/physiopathology/*prevention & 
      control
MH  - Myocardium/*enzymology/pathology
MH  - Necrosis
MH  - Obesity/blood/*complications/physiopathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Time Factors
MH  - Ventricular Function, Left
MH  - Ventricular Pressure
MH  - Ventricular Remodeling
MH  - Weight Gain
PMC - PMC4469881
OTO - NOTNLM
OT  - diet-induced obesity
OT  - heart failure
OT  - mammalian target of rapamycin
OT  - metabolic syndrome
OT  - myocardial infarction
OT  - transgenic mice
EDAT- 2015/04/19 06:00
MHDA- 2015/09/22 06:00
PMCR- 2016/06/15
CRDT- 2015/04/19 06:00
PHST- 2015/01/07 00:00 [received]
PHST- 2015/04/10 00:00 [accepted]
PHST- 2015/04/19 06:00 [entrez]
PHST- 2015/04/19 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
PHST- 2016/06/15 00:00 [pmc-release]
AID - ajpheart.00008.2015 [pii]
AID - H-00008-2015 [pii]
AID - 10.1152/ajpheart.00008.2015 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2015 Jun 15;308(12):H1530-9. doi: 
      10.1152/ajpheart.00008.2015. Epub 2015 Apr 17.