A role for suppressed bone formation favoring catch-up fat in the pathophysiology of catch-up growth after food restriction.

Purpose: Catch-up growth is always companied with later development of obesity and osteoporosis that are two interrelated clinical entities. However, the potential mechanism of the link between them during catch-up growth is unknown. Methods: Rats were divided into two groups. Rats of the normal control (NC) group were offered ad libitum access to food, while rats of CUGFR group were food restricted for 4 weeks, and then were allowed full access to food for 0, 2, 4 weeks, respectively. The fat percentage and distribution, bone mineral density, biochemical and histological indexes of bone were detected. Moreover, the expression of adipogenic or osteoblastic differentiation-related genes of mesenchymal stem cells (MSCs) was also determined. Results: Catch-up growth led to a rapid visceral fat accumulation. Although there was no difference in the histological indexes of bone between NC group and CUGFR group, the bone turnover marker, serum Bone Gla-protein (s-BGP), decreased in CUGFR group. The adipogenic differentiation-related gene of MSCs, PPAR-gamma, was significantly higher than that of NC group especially when catch-up growth for 4 weeks. Nevertheless, the osteoblastic differentiation-related gene of MSCs, Runx2, was increased but failed to reach the levels of the controls eventually. Both protein and mRNA of TAZ, a main transcriptional modulator of MSCs differentiation, failed to catch up even after being allowed full access to food for 4 weeks. Conclusion: CUGFR induces the differential differentiation of MSCs, potentially suppressing bone formation and favoring catch-up fat, which might be responsible for the increased risk of osteoporosis and obesity during CUGFR. [ABSTRACT FROM AUTHOR]