Food-restriction in obese dyslipidaemic diabetic mice partially restores basal contractility but not contractile reserve.
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.
Van den Bergh
An
A
Department of Cardiovascular Diseases, Division of Experimental Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
Vangheluwe
Peter
P
Vanderper
Annelies
A
Carmeliet
Peter
P
Wuytack
Frank
F
Janssens
Stefan
S
Flameng
Willem
W
Holvoet
Paul
P
Herijgers
Paul
P
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
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium