Parental obesity and health of offspring: a role for the father? (#179)
Obesity is epidemic in Australia and internationally and it is now the most important factor contributing to the overall burden of disease. While adult obesity has major health consequences, including an increased risk of cardiovascular disease, type 2 diabetes and cancer, it is now clear that obesity in parents has adverse consequences for the health of their offspring. It is well established in humans and other species that maternal overweight and obesity is linked to obesity and impaired metabolic health and other conditions in offspring, through ‘developmental programming’, in addition to shared genetics and environment. Programming of offspring phenotype by the obese mother through effects on the ovarian, periconceptional or uterine environment and the biological pathways involved, are being increasingly documented. Recently, paternal exposures or conditions, including obesity, have emerged as also able to developmentally program health of offspring. While being overweight or obese is common in women of reproductive age and in those who are pregnant, the prevalence is even higher in men, including those of reproductive age; 41.7% in men aged 18-24 years, rising to 74.1% in those aged 35-44 years (compared to 35% and 55.3% respectively in women) in 2011. Using rodents, we have established directly that paternal obesity impairs reproductive and metabolic health in offspring, in terms of obesity, insulin resistance and impaired glucose tolerance, with intergenerational transmission to the second generation through both parental lines. Altered metabolic and hormonal state and oxidative stress are implicated as initiating this programming by paternal obesity, with altered sperm non coding RNAs, including microRNAs, being candidate paternal signals of obesity to offspring. Importantly, in mice, short term exercise and diet interventions at least partly ameliorate the abnormal metabolic and hormonal state and sperm function of the obese male. Such interventions are therefore options for evaluation in the prevention of paternal obesity initiation of intergenerational transmission and amplification of obesity and metabolic disease and infertility.