Is Reduced Adiponectin mRNA Associated with Alterations in Transcription Factor ATF3 in Adipose Tissue of Nutritionally Programmed Microswine Offspring?

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Poor prenatal and accelerated postnatal growth is associated with elevated cardiometabolic risk in adulthood, but underlying mechanisms are unknown. We previously showed that microswine offspring whose mothers ate a low protein diet (low protein offspring, LPO) exhibited lower adipose tissue (AT) mRNA levels for adiponectin, a cardiometabolically protective hormone, vs. normal protein offspring (NPO) controls. LPO also exhibit hyperreactivity to norepinephrine in vasculature. Therefore, we hypothesized that increased sensitivity to β adrenergic receptors (βAR) in AT causes low adiponectin mRNA level in LPO, and that this is mediated by increases in both CREB, an effector of βAR signaling, and CREB’s downstream transcriptional repressor of adiponectin, ATF3. Nuclear proteins and total mRNA were isolated from AT of juvenile LPO and NPO; dot blot and real-time PCR were used to analyze ATF3 and CREB nuclear protein and mRNA, respectively. ATF3 and CREB mRNA levels were reduced in LPO vs. NPO in subcutaneous (SC)-AT, but not in intra-abdominal (ABD)-AT. There was no difference in phosphorylated CREB level based on maternal diet, post-weaning diet, or sex. In ABD-AT, ATF3 mRNA was reduced by post-weaning caloric restriction (CR) in NPO; LPO-CR had higher ATF3 mRNA than NPO-CR. CR also reduced ATF3 in NPO, but not in LPO, in SC-AT. ATF3 protein in ABD-AT was 2.4 times higher in male LPO than in male NPO, though this difference was not statistically significant. Because patterns of ATF3 and CREB do not match those predicted, the βAR system is probably not responsible for reductions in adiponectin mRNA levels.




Adiponectin, Fetal Programming, Transcription Factors

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