title: Caloric restriction ameliorates cardiomyopathy in animal model of diabetes.
abstract: BACKGROUND
  The db/db mouse is an animal model of diabetes in which leptin receptor activity is deficient resulting accelerated cardiomyopathy when exposed to angiotensin (AT). Toll-like receptors 4 and 2 (TLR4, TLR2) are pattern recognition receptors, that recognize pathogen-associated molecular patterns and exacerbate and release inflammatory cytokines. Fetuin A (Fet A) is a fatty acid carrier which affects inflammation and insulin resistance in obese humans and animals through TLRs. The aim of this study was to investigate the effect of caloric restriction (CR) on free fatty acids (FFA) level and the inflammatory response in diabetic cardiomyopathy.
  
  
  RESULTS
  Left ventricular hypertrophy, increased fibrosis and leukocytes infiltration were observed in db/db AT treated hearts. Serum glucose, FFA, and cholesterol levels were elevated in db/db AT treated mice. Cardiac expression of PPARα increased while AKT phosphorylation was decreased.
  
  
  CONCLUSIONS
  Cumulatively, CR elevated cardiac PPARα improved the utilization of fatty acids, and reduced myocardial inflammation as seen by reduced levels of Fet A. Thus CR negated cardiomyopathy associated with AT in an animal model of diabetes suggesting that CR is an effective therapeutic approach in the treatment of diabetes and associated cardiomyopathy.
authors.affiliation: Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel; Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Cohen
authors.affiliation: Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel; Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Waldman
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Laniado-Schwartzman
authors.affiliation: Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel.
authors.forename: Danny
authors.initials: D
authors.lastname: Gurfield
authors.affiliation: Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Aravot
authors.affiliation: Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Arad
authors.affiliation: Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Israel. Electronic address: hochhaus@post.tau.ac.il.
authors.forename: Edith
authors.initials: E
authors.lastname: Hochhauser
mesh_terms: D000818:Animals; D031204:Caloric Restriction / Q000379:methods; D009202:Cardiomyopathies / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D047493:PPAR alpha
keywords: AKT; Caloric restriction; Fetuin-A; Free fatty acids; PPARα; TLR2; TLR4; TNF-α; db/db mice