Transgenerational inheritance of metabolic disease may be a strong contributor to the global obesity epidemic. While the impact of maternal obesity on offspring metabolism is well documented, strong evidence for an influence of paternal obesity is just emerging. Our group was one of the first to demonstrate that paternal obesity confers metabolic changes to the female offspring (Ng et al, 2010). Here we show that the male offspring are also impacted by their father’s metabolic status.
Sprague-Dawley rat fathers were fed either a control diet (CD-F0) or a high fat diet (HFD-F0) for 14 weeks before being mated with control females. The male offspring were weaned onto a control diet and killed either at 8 weeks or 6 months of age.
Five weeks after weaning, the males from HFD-F0 showed a slow down in growth resulting in a significantly lower body weight from 9 weeks to 6 months of age. A decrease in plasma level of growth hormone and IGF1 was detected in 8 week old rats from HFD-F0. These rats presented smaller fat pads with a decrease in expression of Pparg and Igf1r in retro-peritoneal fat. In parallel, a decrease in expression of genes involved in muscle growth (Ghr, Igf1, mTOR and MyoD) was observed in tibialis anterioris muscle of males from HFD-F0. This resulted in smaller animals at 6 months of age that had smaller fat pads and muscles. The muscles of these rats showed ectopic lipid deposition with an increased expression of genes driving lipogenesis (Srebf1 and Fasn).
The changes in growth and metabolism appeared to have no impact on glucose tolerance of 6 months old offspring. As observed in other models of programming (e.g. maternal low protein diet), investigating later stages of adulthood may uncover more direct metabolic consequences indicative of disease.