title: Restriction of food intake prevents postinfarction heart failure by enhancing autophagy in the surviving cardiomyocytes.
abstract: We investigated the effect of restriction of food intake, a potent inducer of autophagy, on postinfarction cardiac remodeling and dysfunction. Myocardial infarction was induced in mice by left coronary artery ligation. At 1 week after infarction, mice were randomly divided into four groups: the control group was fed ad libitum (100%); the food restriction (FR) groups were fed 80%, 60%, or 40% of the mean amount of food consumed by the control mice. After 2 weeks on the respective diets, left ventricular dilatation and hypofunction were apparent in the control group, but both parameters were significantly mitigated in the FR groups, with the 60% FR group showing the strongest therapeutic effect. Cardiomyocyte autophagy was strongly activated in the FR groups, as indicated by up-regulation of microtubule-associated protein 1 light chain 3-II, autophagosome formation, and myocardial ATP content. Chloroquine, an autophagy inhibitor, completely canceled the therapeutic effect of FR. This negative effect was associated with reduced activation of AMP-activated protein kinase and of ULK1 (a homolog of yeast Atg1), both of which were enhanced in hearts from the FR group. In vitro, the AMP-activated protein kinase inhibitor compound C suppressed glucose depletion-induced autophagy in cardiomyocytes, but did not influence activity of chloroquine. Our findings imply that a dietary protocol with FR could be a preventive strategy against postinfarction heart failure.
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takatomo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University School of Dentistry, Mizuho, Japan. Electronic address: gt@dent.asahi-u.ac.jp.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsujimoto
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogino
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takeyama
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ushikoshi
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mikami
authors.affiliation: Department of Food and Nutrition, Sonoda Women's University, Amagasaki, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Hyogo Prefectural Amagasaki Hospital, Amagasaki, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D064752:Atrial Remodeling; D001343:Autophagy; D015153:Blotting, Western; D001835:Body Weight; D006328:Cardiac Catheterization; D002470:Cell Survival; D002478:Cells, Cultured; D003720:Densitometry; D005508:Food Deprivation; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D008247:Lysosomes / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009929:Organ Size; D015398:Signal Transduction; D014463:Ultrasonography; D014617:Vacuoles / Q000473:pathology / Q000648:ultrastructure
chemical_list: D000255:Adenosine Triphosphate