Neonatal food restriction permanently alters rat body dimensions and energy intake

Neonatal food restriction (FR) in rats, by means of increased litter size, has been used as a model for developmental programming by several investigators. However, the results reported have been inconsistent and difficult to compare between studies. In the present study, we aim to characterize the effects of this model throughout life in both sexes of one particular strain. On the second day of life, Wistar rat pups were randomly assigned to a litter of 10 (control) or 20 (FR). All litters had an equal number of males and females, and pups were weaned on day 25. Body dimensions and food intake were measured regularly until the age of one year. Serum leptin levels were determined in four subsets of different ages. FR acutely reduced growth in all body dimensions and serum leptin levels. Despite catch-up after weaning, all these parameters remained reduced throughout life. Male and female FR rats had a significantly reduced absolute energy intake throughout life. Male FR rats had significantly higher energy intake adjusted for body weight immediately after weaning. During catch-up growth, both FR males and females showed significantly enhanced feed efficiency. These results suggest that neonatal food restriction programmed both male and female Wistar rats to remain small and lean in adult life, with a lower food intake. Low neonatal leptin levels may play a mechanistic role in this process.