Postnatal overfeeding in rats leads to moderate overweight and to cardiometabolic and oxidative alterations in adulthood

In contrast to the masses of data on obesity, few data are available concerning the cardiometabolic and oxidative consequences of moderate overweight. The model of postnatal overfeeding (OF) induces an increase in body weight at weaning that remains during adult life. Litters of Wistar rats were either maintained at 12 pups (normal-fed group, NF), or reduced to 3 pups at birth in order to induce OF. At 6 months of age, metabolic parameters, circulating oxidative stress and aortic and coronary vasoreactivity were assessed. Cardiac susceptibility to ischemia-reperfusion injury was also evaluated ex vivo as were markers of cardiac remodeling. OF led to an increase in body weight at weaning (+50%); the increase in body weight persisted throughout adult life, but was less marked (+10%). Significant increases in plasma levels of fasting glucose, insulin and leptin were found in OF rats. An increase in both plasma hydroperoxides and cardiac superoxide dismutase activity and a decrease in plasma ascorbate were found in OF rats. Vasoreactivity was not modified, but ex vivo, after 30 min of ischemia, isolated hearts from OF rats showed lower recovery of coronary flow along with a greater release of LDH. Studies on heart tissues showed an increase in collagen content and increased expression and activity of MMP-2. Our findings show that moderate overweight in adult rats, induced by postnatal overfeeding, leads to both metabolic and oxidative disturbances as well as a higher susceptibility to cardiac injury after ischemia ex vivo, which may be explained, at least in part, by ventricular remodeling. ► Overfeeding rats just after birth induces early and permanent moderate overweight. ► Moderately overweight adult rats have impaired metabolic markers. ► Moderately overweigh adult rats have increased markers of oxidative stress. ► Hearts of these rats have a higher susceptibility to ischemia-reperfusion injury. ► Hearts of moderately overweight rats show aspects of remodeling.