A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic insulin-like growth factor 1 (Igf1) expression, leading to impaired growth and metabolism. Previously we have demonstrated that the timing of nutritional restoration in perinatal life can differentially programhepatic gene expression. While micro RNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3i-UTR of Igf1, we examined how proteins restoration in maternal protein restricted rat (MPR) offspring influences hepatic miR-29 and Igf1 expression in adulthood. Pregnant Wistar rats were designated into one of four dietary regimes; 20% protein (Control), 8% protein during lactation only (LP-Lact), 8% protein during gestation only (LP1) or both (LP2). The steady-state expression of hepatic miR-29 mRNA significantly increased in LP2 offspring at postnatal day 21 and 130 and this was inversely related tohepatic Igf1 mRNA and body weight. Interestingly, this reciprocal association was stronger inLP-Lact offspring at postnatal day 21. Functional relevance of this in vivo relationship was evaluated by transfection of miR-29 mimics in neonatal clone 9 rat hepatoma cells. Transfection with miR-29suppressed Igf1 expression by 12 hours. Collectively, these findings implicate that nutritional restoration post-weaning (after liver differentiation) in MPR rat offspring fails to prevent long-term impaired growth, in part, due to miR-29 suppression of hepatic Igf1 expression.
Available at: http://works.bepress.com/daniel-hardy/14/