Postnatal Overfeeding in Rodents by Litter Size Reduction Induces Major Short- and Long-Term Pathophysiological Consequences

Abstract

AbstractNumerous studies have demonstrated that the early postnatal environment can influence body weight and energy homeostasis into adulthood. Rodents raised in small litters have been shown to be a useful experimental model to study the short- and long-term consequences of early overnutrition, which can lead to modifications not only in body weight but also of several metabolic features. Postnatal overfeeding (PNOF) induces early malprogramming of the hypothalamic system, inducing acquired persisting central leptin and insulin resistance and an increase in orexigenic signals. Visceral white adipose tissue, lipogenic activity, and inflammatory status are increased in PNOF rodents, while brown adipose tissue shows reduced thermogenic activity. Pancreatic and hepatic glucose responsiveness is persistently reduced in PNOF rodents, which also frequently present disturbances in plasma lipids. PNOF rodents present increased circulating concentrations of leptin, elevated corticosterone secretion, and significant changes in glucocorticoid sensitivity. PNOF also influences nephrogenesis and renal maturation. Increased oxidative stress is also described in circulating blood and in some tissues, such as the heart or liver. At the cardiovascular level, a moderate increase in arterial blood pressure is sometimes observed and rapid cardiac hypertrophy is observed at weaning; however, during maturation, impaired contractility and fibrosis are observed. Myocardial genome expression is rapidly modified in overfed mice. Moreover, hearts of PNOF rodents are more sensitive to ischemia-reperfusion injury. Together, these results suggest that the nutritional state in the immediate postnatal period should be taken into account, because it may have an impact on cardiometabolic risk in adulthood.