Bone marrow-derived mesenchymal stem cells are driven to a more adipogenic phenotype in the intra uterine growth restricted fetus contributing to offspring obesity.

摘要

The molecular mechanisms underlying childhood obesity remain incompletely understood, precluding any reliable predictive biomarkers or targeted molecular interventions. We used Maternal Food Restriction (MFR) rat model and isolated Bone Marrow Derived Stem Cells (BMDSCs) to determine mechanistic insights. We found markedly enhanced mRNA and protein levels for adipogenic molecular markers such as PPARgamma, C/EBPalpha, ADRP, Srebf1, LPL and adiponectin in the MFR compared to the control group (p<0.05). In contrast, Wnt signaling markers such as LRP5, beta-catenin, GSK2 and LEF1 were decreased at both mRNA and protein levels (p<0.05) in MFR. Further, adipogenesis-related miR-30d showed 30-fold increase in MFR and the adipocyte differentiation potential was 5 fold higher under induction. Mir-30d and the early transcription factor ZFP521 suppressed RUNX2, enhancing PPARgamma expression in MFR. We conclude that markedly enhanced adipogenic molecular and functional profiles in MFR suggest a likely link between intrauterine nutritional stress and later offspring obesity.