Maternal nutrition during pregnancy has been found to have a significant impact upon the health of offspring after maturation. However, strategies for modulation of metabolism without an adverse effect on the fetus have remained limited. It was recently shown that maternal high calorie diet induces obesity in later life of the offspring, and maternal oral administration of uncarboxylated osteocalcin (GluOC), which crosses the placenta, improves metabolic status in the offspring by unknown mechanism. 
We thus explored the molecular mechanisms for the effect of maternal high calorie diet and GluOC during gestation on metabolic properties of the offspring. From our results, a maternal high-fat, high-sucrose diet during pregnancy causes metabolic disorders in the liver of the offspring due to hypermethylation of the Pygl gene, encoding glycogen phosphorylase L, which mediates hepatic glycogenolysis. The lower expression of Pygl induced by the maternal diet causes the hepatic accumulation of glycogen and triglyceride in the offspring, which remains in adulthood. On the other hand, maternal GluOC upregulates Pygl expression in the offspring via both direct and indirect pathways to improve maternal diet-induced obesity and abnormal energy metabolism.
We propose that maternal high calorie diet is reflected in the hepatic glycogenolysis capacity of the offspring via epigenetic modification of Pygl and maternal oral administration of GluOC protects the offspring from metabolic disorders induced by maternal diet by regulation of glycogenolysis.