Food-restriction in obese dyslipidaemic diabetic mice partially restores basal contractility but not contractile reserve
1 Department of Cardiovascular Diseases, Division of Experimental Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium
2 Department of Molecular Cell Biology, Laboratory of Physiology, Katholieke Universiteit Leuven, Leuven, Belgium
3 Department of Molecular and Cellular Medicine, Vesalius Research Center, Katholieke Universiteit Leuven, Leuven, Belgium
4 Department of Cardiovascular Diseases, Cardiology, Katholieke Universiteit Leuven, Leuven, Belgium
5 Department of Cardiovascular Diseases, Atherosclerosis and Metabolism Unit, Katholieke Universiteit Leuven, Herestraat 49, Leuven 3000, Belgium
* Corresponding author. Tel: +32 16 344 621, Fax: +32 16 344 616, Email: paul.herijgers{at}med.kuleuven.be
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Abstract |
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Aims: 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.
Methods and 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) Ca2+ 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 Ca2+ 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.
Conclusion: 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.
Key Words: Contractility • Cardiac reserve • Obesity • Type II diabetes • Diet
Received May 11, 2009; Revised September 16, 2009; Accepted September 22, 2009