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Accelerated growth during infancy alters bone characteristics and the activity of mesenchymal stem cells (MSC) in neonatal piglets

Rapid growth during infancy has been associated with increased risk of childhood obesity. We examined the effects of increased growth rate caused by overfeeding on growth, bone integrity, and activity of MSC in neonatal piglets. Limit fed (LF) animals received a standard piglet milk replacer at a rate to achieve normal growth, while the overfed (OF) group voluntarily consumed nearly 60% more of the same diet for 21 days. Overfed piglets had higher growth rate (P < 0.001) and feed intake (P < 0.05), and lower feed efficiency (P < 0.001) compared to LF piglets. The OF animals had heavier, larger bones with greater bone mineral content than the LF group (P < 0.05). Surprisingly, MSC isolated from OF animals adopted an adipocytic lineage less readily than those isolated from LF animals after induction with adipocytic media. This was indicated by lower gene expression of PPARG, LPL and AP2 (P < 0.05) as well as by decreased lipid accumulation determined by Oil Red O staining. Increased (P < 0.2) gene expression of Runx2 following osteogenic induction was also seen in MSC from OF pigs. Accelerated growth during infancy led to a decreased response of MSC to an adipocytic environment, as well as an increased response to osteogenic induction. These results indicate the potential for neonatal dietary interventions to influence growth and body composition later in life via programming of MSC.