PMID- 18040027 OWN - NLM STAT- MEDLINE DCOM- 20080109 LR - 20220408 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 116 IP - 24 DP - 2007 Dec 11 TI - Cardioprotective effects of short-term caloric restriction are mediated by adiponectin via activation of AMP-activated protein kinase. PG - 2809-17 AB - 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. METHODS AND 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. FAU - Shinmura, Ken AU - Shinmura K AD - 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 FAU - Tamaki, Kayoko AU - Tamaki K FAU - Saito, Kiyomi AU - Saito K FAU - Nakano, Yasuko AU - Nakano Y FAU - Tobe, Takashi AU - Tobe T FAU - Bolli, Roberto AU - Bolli R LA - eng GR - HL-55757/HL/NHLBI NIH HHS/United States GR - HL-70897/HL/NHLBI NIH HHS/United States GR - HL-76794/HL/NHLBI NIH HHS/United States GR - HL-78825/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20071126 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Adiponectin) RN - EC 2.7.4.3 (Adenylate Kinase) SB - IM CIN - Circulation. 2007 Dec 11;116(24):2779-81. PMID: 18071087 MH - Adenylate Kinase/*metabolism MH - Adiponectin/*physiology MH - Animals MH - *Diet, Reducing MH - Disease Models, Animal MH - Humans MH - Mice MH - Mice, Transgenic MH - Myocardial Ischemia/*diet therapy/enzymology/*physiopathology MH - Obesity/prevention & control EDAT- 2007/11/28 09:00 MHDA- 2008/01/10 09:00 CRDT- 2007/11/28 09:00 PHST- 2007/11/28 09:00 [pubmed] PHST- 2008/01/10 09:00 [medline] PHST- 2007/11/28 09:00 [entrez] AID - CIRCULATIONAHA.107.725697 [pii] AID - 10.1161/CIRCULATIONAHA.107.725697 [doi] PST - ppublish SO - Circulation. 2007 Dec 11;116(24):2809-17. doi: 10.1161/CIRCULATIONAHA.107.725697. Epub 2007 Nov 26.