Maternal high-fat diet induces hyperproliferation and alters Pten/Akt signaling in prostates of offspring.

Developing recommendations for prostate cancer prevention requires identification of modifiable risk factors. Maternal exposure to high-fat diet (HFD) initiates a broad array of second-generation adult disorders in murine models and humans. Here, we investigate whether maternal HFD in mice affects incidence of prostate hyperplasia in offspring. Using three independent assays, we demonstrate that maternal HFD is sufficient to initiate prostate hyperproliferation in adult male offspring. HFD-exposed prostate tissues do not increase in size, but instead concomitantly up-regulate apoptosis. Maternal HFD-induced phenotypes are focally present in young adult subjects and greatly exacerbated in aged subjects. HFD-exposed prostate tissues additionally exhibit increased levels of activated Akt and deactivated Pten. Taken together, we conclude that maternal HFD diet is a candidate modifiable risk factor for prostate cancer initiation in later life.