Postnatal undernutrition alters adult female mouse cardiac structure and function leading to limited exercise capacity

Abstract Adults who experienced undernutrition during criticalwindows of development are at increased risk for cardiovascular disease. The contribution of cardiac function to this increased disease risk is uncertain.We evaluated the effect of a short episode of postnatal undernutrition on cardiovascular function in mice at the whole animal, organ, and cellular levels. Pups born to control mouse dams were suckled from birth to postnatal day (PN) 21 on dams fed either a control (20% protein) or a low protein (8% protein) isocaloric diet. After PN21 offspring were fed the same control diet until adulthood. At PN70 ˙VO2,max was measured by treadmill test. At PN80 cardiac function was evaluated by echocardiography and Doppler analysis at rest and following β-adrenergic stimulation. Isolated cardiomyocyte nucleation and Ca2+ transients (with and without β-adrenergic stimulation) were measured at PN90. Female mice that were undernourished and then refed (PUN), unlike malemice, had disproportionately smaller hearts and their exercise capacity, cardiac diastolic function, and heart rate responsiveness to adrenergic stimulation were limited. A reduced left ventricular end diastolic volume, impaired early filling, anddecreased stored energy at the beginning of diastole contributedto these impairments. Female PUN mice had more mononucleated cardiomyocytes; under resting conditions binucleated cells had a functional profile suggestive of increased basal adrenergic activation. Thus, a brief episode of early postnatal undernutrition in the mouse can produce persistent changes to cardiac structure and function that limit exercise/functional capacity and thereby increase the risk for the development of a wide variety of cardiovascular morbidities.