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.