title: Short-term caloric restriction in db/db mice improves myocardial function and increases high molecular weight (HMW) adiponectin.
abstract: BACKGROUND
  Obesity and metabolic syndrome lead to the development of metabolic heart disease (MHD) that is characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and increased mitochondrial ROS. Caloric restriction (CR) is a nutritional intervention that protects against obesity, diabetes, and cardiovascular disease. Healthy adipose tissue is cardioprotectiveviareleasing adipokines such as adiponectin. We tested the hypothesis that CR can ameliorate MHD and it is associated with improved adipose tissue function as reflected by increased circulating levels of high molecular weight (HMW) adiponectin and AMP-activated protein kinase (AMPK) indb/dbmice.
  
  
  METHODS
  Genetically obesedb/dband leandb/+male mice were fed eitherad libitumor subjected to 30% CR for 5 weeks. At the end of the study period, echocardiography was carried out to assess diastolic function. Blood, heart, and epididymal fat pads were harvested for mitochondrial study, ELISA, and Western blot analyses.
  
  
  RESULTS
  CR reversed the development of LVH, prevented diastolic dysfunction, and decreased cardiac mitochondrial H2O2indb/db(vs. ad lib) mice. These beneficial effects on the heart were associated with increased circulating level of HMW adiponectin. Furthermore, CR increased AMPK and eNOS activation in white adipose tissue ofdb/dbmice, but not in the heart.
  
  
  CONCLUSIONS
  These findings indicate that even short-term CR protects the heart from MHD. Whether the beneficial effects of CR on the heart could be related to the improved adipose tissue function warrants future investigation.
authors.affiliation: Diabetes and Metabolism Unit, Section of Endocrinology, Department of Medicine, Boston University Medical Center, Boston, Massachusetts.
authors.forename: X Julia
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Diabetes and Metabolism Unit, Section of Endocrinology, Department of Medicine, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Erma
authors.initials: E
authors.lastname: Babo
authors.affiliation: Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Fuzhong
authors.initials: F
authors.lastname: Qin
authors.affiliation: Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Dominique
authors.initials: D
authors.lastname: Croteau
authors.affiliation: Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
keywords: AMPK; adipose tissue; caloric restriction; metabolic heart disease