Early life exposure to a high fat diet results in histological and molecular changes in the prostate which are transmitted to second generation offspring through the father (#159)
A high fat diet (HFD) during pregnancy is associated with high birth weight offspring and a high birth weight is associated with adult obesity. Obesity is associated with an increased risk of metabolic and cardiovascular disorders and cancer, including prostate cancer. We investigated if early life exposure to a HFD results in changes in the prostate that may be indicative of an increased risk of cancer in adulthood. Female rats were fed a control (7% total fat) or HFD (23% total fat) from 2 weeks before mating and during pregnancy. All dams received a control diet after giving birth. Offspring from control dams were either fed a control diet until day 100 (control group) or a HFD until puberty (day 50) followed by a control diet until day 100 (prepubertal HFD group). Offspring from HFD dams were fed a control diet until day 100 (maternal HFD group). First generation males were mated with females exposed to a standard diet to generate second generation male offspring that were only exposed to standard chow throughout life. Prostates were collected from male offspring at day 100. In the first generation, there was an increased incidence of prostate hyperplasia in offspring from the maternal HFD group (P=0.0142). An increase in hyperplasia was also seen in second generation males (P<0.001). Expression of genes involved in prostate cancer (Ar, Cdh) and epigenetics/imprinting (Dnmt1, Dnmt3a, Dnmt3b, Igf2r, Ctcf, Plagl1) were significantly altered in the prostate from first and second generation males. We have shown for the first time, in the rat, which spontaneously develops prostate cancer with age that an early life exposure to a HFD induces histological and molecular changes in the prostate of offspring which may predispose them to an increased risk of cancer in adulthood; and these changes were transmitted to second generation males.