Effects of Neonatal Supplemental Oxygen and High Fat Diet on Weight Gain, Ventricular Hypertrophy and Contractility

Premature birth represents about 13% of live births each year. Since lungs of these infants are underdeveloped, they receive supplemental oxygen right after birth, but little is known about its effects on the development of normal physiological responses and whether it impacts long-term cardio-metabolic function. Based on previous studies from our lab that showed increased pulse wave velocity in 12 month old rats exposed to neonatal supplemental oxygen, we hypothesized that neonatal exposure to supplemental oxygen causes cardiac hypertrophy and decreased left ventricular contractility. We also hypothesized that these effects to supplemental oxygen would be enhanced by 10 weeks on a high fat diet. To test the hypothesis, we used our rat model of 80% and 21% O2 exposed rats to FlO2=0.80 and 0.21 respectively, for 8 days post-birth. Two months after birth, these 80% and 21% rats were randomly assigned to either a high fat diet (60% of calories from animal fat) or low fat diet (CON) for 10 weeks during which their weights and caloric consumption were monitored. After 10 weeks, a Miller conductance catheter was inserted into the left ventricle to obtain pressure-volume loops and end-systolic pressure volume relationship, which was used to evaluate contractility. 80% rats exposed to CON diet showed higher cumulative weight gain than 21% rats on the same diet. No significant difference was observed between the weights of the left ventricles due to exposure to supplemental oxygen or high fat diet. Neonatal supplemental oxygen exposure decreased contractility whereas the combination of high fat diet and supplemental oxygen exposure reversed this effect. These data suggest that neonatal exposure to supplemental oxygen promotes weight gain and decreased ventricular contractility

Neonatal Supplemental Oxygen Exposure Promotes the Development of Metabolic Disease in Adult Rats

Premature infants frequently require supplemental oxygen to sustain life, but little is known about how supplemental oxygen administered during the critical developmental window after birth increases the risk of age-related disease, including obesity and diabetes. We hypothesized that neonatal rats exposed to supplemental oxygen (OXY) would have impaired glucose tolerance and that they would develop a diabetes phenotype earlier than controls (CON), when offered a high fat diet. We used an established rat model of neonatal oxygen exposure (80% O2 for 8-14 days) and glucose tolerance was evaluated 14 days and 12 months post-natally. To evaluate glucose tolerance, baseline blood glucose was measured after an overnight fast, followed by an intraperitoneal injection of concentrated glucose. Blood glucose was then measured 15, 30, 60 and 120 minutes post-injection. In a second experiment, two month old OXY and CON rats were randomly assigned to an animal-based fat diet (60% of calories from fat), or standard, low fat diet for ten weeks. At the beginning of the study and each subsequent week, glucose tolerance was measured. At 14 days and 12 months, OXY rats had higher blood glucose at 15 and 30 minutes compared to CON rats. OXY rats fed a high fat diet developed frank glucose intolerance after 4 weeks. Ten weeks of high fat diet had minimal effect on glucose tolerance in CON rats. Taken together, these data suggest that supplemental oxygen during the neonatal period may predispose the premature infant to the development of metabolic disease later in life