Maternal Mice Fed High-Fat Diet Produce Larger Pups

University of Pennsylvania researchers found that pregnant mice fed a high-fat diet produce pups that are longer, weigh more, and have reduced insulin sensitivity -- factors that indicate a risk for obesity and diabetes. Interestingly, despite the lack of further high-fat diet exposure, the traits of increased body length and insulin insensitivity persisted into the second generation.

Subsequent investigation found that the changes in gene expression responsible for alterations in body length and insulin insensitivity were sex-dependent. Only female offspring exhibited evidence of altered programming of the growth hormone axis, a gene pathway that controls overall growth and metabolism.

This work adds to the growing body of research in epigenetics, the study of heritable alterations in gene expression that act independently of changes in DNA sequence. Until very recently, scientists believed that our genes were the sole carrier of hereditary information. However, in addition to inheriting genes from our parents, we can also inherit their epigenetic "switches" that turn our genes on or off. These switches can be flipped by our environments and experiences to help us adapt to challenges put before us, and can be passed from generation to generation.

"Much research has focused on identifying genes (our developmental 'hardware') as predisposing factors for obesity. However, it turns out that epigenetics (our developmental 'software') likely makes a much larger contribution by dictating how our genes are actually utilized," said Tracy Bale, PhD, the study's senior author. "We found compelling evidence that the evolutionarily critical trait of body size can be modulated by maternal diet across at least two generations. In the end, you may not only be what you eat, but what your grandmother ate."

Research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.