Aim: There is evidence that paternal obesity confers metabolic changes to offspring (¹ Ng et al, 2010). Our group was one of the first to demonstrate such changes, reporting female offspring of obese fathers had dysregulated glucose metabolism and insulin secretion at 6 and 12 weeks of age. This follow up cohort determined the long term consequences of paternal obesity by studying females at an older age and females challenged with a high fat diet (HFD).
Method: Obese and control groups (n=8,8) of F0 males (HFD/CON F0) were established by feeding male Sprague Dawley rats either a control or HFD from 3-13 weeks of age prior to mating with females maintained on control diet. The resulting F1 female offspring were weaned and maintained on control or HFD. The female offsprings’ phenotype (insulin/glucose metabolism, growth etc.) was investigated at 12 and 26 weeks.
Results: The birth weight of paternal HFD F1 female offspring was smaller than CON F1 (6.1 ± sd 0.3; 6.9 ± sd 0.8), however when weaned onto control diet they had the same pattern of growth. Interestingly, when weaned onto HFD, paternal HFD daughters had a reduced growth and were smaller at 26 weeks. At 6 weeks the paternal HFD daughters showed evidence of impaired insulin response regardless of postnatal diet, with some evidence of impaired glucose tolerance in those fed HFD. This impaired phenotype did not persist to 26 weeks in the control fed daughters and paradoxically HFD fed daughters had improved glucose/insulin metabolism despite insufficient insulin secretion.
Conclusion: Paternal obesity confers metabolic changes to daughters, which are modulated by the postnatal diet the daughters consume. This complex programmed phenotype of the daughters from obese fathers warrants further investigation of the underlying molecular mechanisms. The consequence of this phenotype needs to be determined in aged animals.