| Description |
Intrauterine growth restricted (IUGR) born individuals are at a higher risk for developing obesity and associated co-morbidities in adulthood. An underlying component of these morbidities is adipose dysfunction, with the accumulation of visceral adipose tissue (VAT) in conjunction with an increased expression of peroxisome proliferator activated receptor gamma PPAR?, a proadipogenic factor. Interestingly, in hepatic tissue of the adolescent IUGR female, PPAR? expression displays a decreasing trend. PPAR?'s actions may be mediated by set domain containing histone methyltransferase Setd8 an epigenetic modification enzyme, and direct transcriptional target of PPAR?. In this study, we hypothesize that IUGR will affect mRNA and protein levels of Setd8 in a gender and tissue specific manner in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and hepatic depots before the onset of metabolic disease in postnatal day 21 rats. Uteroplacental insufficiency (UPI) induced IUGR day 21 adipose (SAT and VAT), and hepatic tissue was compared to control tissue using real time RT PCR for mRNA and western blotting for protein levels of Setd8. IUGR increased Setd8 protein levels in visceral adipose tissue of males of and decreased Setd8 protein levels hepatic tissue of females. IUGR did not have a significant effect on SAT mRNA and protein levels. This study demonstrates that IUGR alters Setd8 expression in day 21 rat in a gender and tissue specific manner, consistent with previously observed changes in PPAR? expression, before the onset of metabolic disease and obesity. We speculate that IUGR alters epigenetic gene regulation in adipose and liver, PPAR? and its target enzyme Setd8, and that this may contribute to adult onset obesity observed in this population. |
