title: Food-restriction in obese dyslipidaemic diabetic mice partially restores basal contractility but not contractile reserve.
abstract: OBJECTIVE
  Weight reduction programmes in morbidly obese, diabetic, and hyperlipidaemic subjects usually improve cardiac load and subsequently reverse hypertrophy. However, their effect on contractile dysfunction and impaired cardiac functional reserve is unknown.
  
  
  RESULTS
  The effect of food-restriction-induced weight loss on in vivo cardiac contractility before and during beta-adrenergic stimulation was assessed using left ventricular pressure-volume analysis in a mouse model featuring obesity and Type II diabetes (ob/ob), obesity, Type II diabetes, atherogenic dyslipidaemia, and hypertension (LDLR-/-;ob/ob), or wild-type. In addition, sarcoendoplasmic reticulum (SR) Ca(2+) reuptake, interstitial collagen accumulation, and aortic atherosclerosis were measured. Food-restriction resulted in a 54% lower weight. Weight loss largely normalized pre- and afterload in both ob/ob and LDLR-/-;ob/ob mice. Contractility and relaxation improved after weight loss, partly explained by improved SR Ca(2+) reuptake. Ventricular-vascular stiffening, interstitial collagen accumulation, and aortic atherosclerosis were less in food-restricted than in free-fed LDLR-/-;ob/ob mice. In contrast, cardiac reserve was similarly impaired in free-fed and food-restricted ob/ob and LDLR-/-;ob/ob mice.
  
  
  CONCLUSIONS
  Food-restriction in obese diabetic mice leads to improved cardiac performance by diminishing cardiac load and by ameliorating the intrinsic contractile properties of the cardiac muscle. However, cardiac reserve under dobutamine stimulation did not increase.
authors.affiliation: Department of Cardiovascular Diseases, Division of Experimental Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Van den Bergh
authors.forename: Peter
authors.initials: P
authors.lastname: Vangheluwe
authors.forename: Annelies
authors.initials: A
authors.lastname: Vanderper
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Frank
authors.initials: F
authors.lastname: Wuytack
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Willem
authors.initials: W
authors.lastname: Flameng
authors.forename: Paul
authors.initials: P
authors.lastname: Holvoet
authors.forename: Paul
authors.initials: P
authors.lastname: Herijgers
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D005508:Food Deprivation; D006949:Hyperlipidemias / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000178:diet therapy / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D016277:Ventricular Function, Left; D015431:Weight Loss
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium