Cardioprotective effects of short-term caloric restriction are mediated by adiponectin via activation of AMP-activated protein kinase.
BACKGROUND
Overeating and obesity are major health problems in developed countries. Caloric restriction (CR) can counteract the deleterious aspects of obesity-related diseases and prolong lifespan. We have demonstrated that short-term CR improves myocardial ischemic tolerance and increases adiponectin levels. Here, we investigated the specific role of adiponectin in CR-induced cardioprotection.


RESULTS
Adiponectin antisense transgenic (Ad-AS) mice and wild-type (WT) mice were randomly assigned to a group fed ad libitum and a CR group (90% of caloric intake of ad libitum for 3 weeks, then 65% for 2 weeks). Isolated perfused mouse hearts were subjected to 25 minutes of ischemia, followed by 60 minutes of reperfusion. CR increased serum adiponectin levels by 84% in WT mice. Gel filtration analysis of the oligomeric complex distribution showed that CR produced a marked increase in the high-molecular-weight complex of adiponectin in WT mice; in contrast, CR did not change serum adiponectin levels or their oligomeric pattern in Ad-AS mice. CR improved the recovery of left ventricular function after ischemia/reperfusion and limited infarct size in WT mice; these effects were completely abrogated in Ad-AS mice. CR also increased the phosphorylated form of AMP-activated protein kinase and acetyl-CoA carboxylase in WT but not in Ad-AS mice. Recombinant adiponectin restored CR-induced cardioprotection in Ad-AS mice, and inhibition of AMP-activated protein kinase phosphorylation completely abrogated CR-induced cardioprotection in WT mice.


CONCLUSIONS
The cardioprotective effects of short-term CR are mediated by increased production of adiponectin and the associated activation of AMP-activated protein kinase.
Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan 160-8582. shimmura@sc.itc.keio.ac.jp
Ken
K
Shinmura
Kayoko
K
Tamaki
Kiyomi
K
Saito
Yasuko
Y
Nakano
Takashi
T
Tobe
Roberto
R
Bolli
D000263:Adenylate Kinase / Q000378:metabolism*; D052242:Adiponectin / Q000502:physiology*; D000818:Animals; D004038:Diet, Reducing; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000178:diet therapy* / Q000201:enzymology / Q000503:physiopathology*; D009765:Obesity / Q000517:prevention & control
D052242:Adiponectin; D000263:Adenylate Kinase