Female mice overfed in the first few weeks of life become obese adults - and are much less physically active - than mice that were not overfed as infants, perhaps because of epigenetic changes to DNA in the brain, said researchers from Baylor College of Medicine in a report that appears online in the journal Diabetes.
"We have known for decades that when mice are overfed during the newborn period they tend to stay fatter for their entire lives, but we did not know why," said Dr. Robert Waterland, associate professor of pediatrics - nutrition at BCM and a scientist in the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital. "It was generally thought that animals that are over-nourished in infancy just maintain a higher food intake throughout life."
To test this, Waterland and his colleagues studied mice that were suckled in small litters and compared them to mice suckled in normal sized litters. The mice in the smaller litters had easier access to mom’s milk, and took advantage of it. They became heavier and fatter than the others and remained that way into adulthood, even though all mice were fed the same normal mouse chow after weaning.
Detailed metabolic studies of the adult female mice showed, surprisingly, that those that had been over-nourished as infants did not eat more than their lean counterparts. Instead, they remained fatter as adults because they were much less physically active.
Using special DNA genomic studies, the researchers found there were significant changes in DNA methylation (a post-genetic or epigenetic change) in the hypothalamus area of the brain during infancy (the hypothalamus is a key region for regulation of body weight).
"Infancy is critical period for developmental epigenetics in the mouse hypothalamus," said Waterland. "Overnutrition in infancy is causing persistent changes that last into adulthood. These could mediate the persistent changes in physical activity."
Although the individual methylation changes were small, overall they had a profound effect.
"This underscores the idea that epigenetic changes induced by early nutrition are likely to be subtle," said Waterland. "They are small changes occurring at many different loci in the genome. Cumulatively, however, these may have a major long-term impact on behavior and energy expenditure."
Others who took part in this research include Ge Li, John J. Kohorst, Wenjuan Zhang, Eleonora Laritsky, Govindarajan Kunde-Ramamoorthy, Maria S. Baker and Marta L. Fiorotto, all of BCM.
Funding for this work came from the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK081557) and the U.S. Department of Agriculture - Agricultural Research Service (CRIS 6250-51000-055).