Omentin prevents myocardial ischemic injury through AMP-activated protein kinase- and Akt-dependent mechanisms.
OBJECTIVE
This study examined the impact of omentin on myocardial injury in a mouse model of ischemia/reperfusion (I/R) and explored its underlying mechanisms.


BACKGROUND
Obesity is a major risk factor for ischemic heart disease. Omentin is a circulating adipokine that is down-regulated by obesity.


METHODS
In patients who underwent successful reperfusion treatment after acute myocardial infarction, cardiac function and perfusion defect were assessed by using scintigraphic images. Mice were subjected to myocardial ischemia followed by reperfusion.


RESULTS
This study found that high levels of plasma omentin were associated with improvement of heart damage and function after reperfusion therapy in patients with acute myocardial infarction. Systemic administration of human omentin to mice led to a reduction in myocardial infarct size and apoptosis after I/R, which was accompanied by enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Akt in the ischemic heart. Fat-specific overexpression of human omentin also resulted in reduction of infarct size after I/R. Blockade of AMPK or Akt activity reversed omentin-induced inhibition of myocardial ischemic damage and apoptosis in mice. In cultured cardiomyocytes, omentin suppressed hypoxia/reoxygenation-induced apoptosis, which was blocked by inactivation of AMPK or Akt.


CONCLUSIONS
Our data indicate that omentin functions as an adipokine that ameliorates acute ischemic injury in the heart by suppressing myocyte apoptosis through both AMPK- and Akt-dependent mechanisms.
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yoshiyuki
Y
Kataoka
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: rshibata@med.nagoya-u.ac.jp.
Rei
R
Shibata
Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Koji
K
Ohashi
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takahiro
T
Kambara
Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takashi
T
Enomoto
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yusuke
Y
Uemura
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yasuhiro
Y
Ogura
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Daisuke
D
Yuasa
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kazuhiro
K
Matsuo
Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Takanobu
T
Nagata
Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Toyoharu
T
Oba
Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Hideo
H
Yasukawa
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yasushi
Y
Numaguchi
Department of Cardiology, Ogaki Municipal Hospital, Minaminokawa, Ogaki, Japan.
Takahito
T
Sone
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toyoaki
T
Murohara
Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: nouchi@med.nagoya-u.ac.jp.
Noriyuki
N
Ouchi
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D037102:Lectins / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D051058:Oncogene Protein v-akt / Q000502:physiology*; D062645:Percutaneous Coronary Intervention / Q000379:methods; D010766:Phosphorylation / Q000235:genetics
D015415:Biomarkers; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D051058:Oncogene Protein v-akt; D055372:AMP-Activated Protein Kinases
apoptosis; ischemia; myocytes; omentin; reperfusion