Under-carboxylated osteocalcin regulates glucose and lipid metabolism during pregnancy and lactation in rats

Purpose Under-carboxylated osteocalcin (UcOC), a bone-released hormone is suggested to regulate energy metabolism. Pregnancy and lactation physiological conditions that require high levels of energy. The current study attempts to examine whether UcOC is involved in regulating energy metabolism during these conditions using adult Wistar rats. Methods and results Insulin tolerance tests indicated insulin resistance during late pregnancy (day 19 of pregnancy; P19) and insulin sensitivity during early lactation (day 6 of lactation; L6). Gene expression analyses suggested that muscle glucose metabolism was downregulated during P19 and enhanced during L6. Concomitantly, circulatory UcOC levels were lower during pregnancy but higher during early lactation; the rise in UcOC levels was tightly linked to the lactation process. Altering endogenous UcOC levels pharmacologically with warfarin and alendronate in P19 and L6 rats changed whole-body insulin response and muscle glucose transporter (Glut4) expression. Glut4 expression can be increased by either UcOC or estrogen receptors (ERs), both of which act independent of each other. A high fat diet decreased UcOC levels and insulin sensitivity in lactating rats, suggesting that diet can compromise UcOC-established energy homeostasis. Gene expression of lipid metabolism markers and triglyceride levels suggested that UcOC suppression during early pregnancy is an essential step in maternal lipid storage. Conclusion Taken together, we found that UcOC plays an important role in energy homeostasis via regulation of glucose and lipid metabolism during pregnancy and lactation.