γ-Glutamyl carboxylase in osteoblasts regulates glucose metabolism in mice

• Osteoblast-specific Ggcx conditional knockout (cKO) mice were generated.
• Serum levels of undercarboxylated osteocalcin increased in Ggcx cKO mice.
• The mice could maintain serum glucose levels with low amounts of insulin.
• The weight of white adipose tissue (WAT) decreased in the Ggcx cKO mice.
• GGCX in osteoblasts is involved in regulation of blood glucose and WAT.

Vitamin K-dependent γ-glutamyl carboxylase (GGCX) is an enzyme that catalyzes the conversion of glutamic acid to gamma-carboxyglutamic acid in substrate proteins. Among GGCX target proteins, recent evidence indicates that osteocalcin regulates insulin sensitivity and secretion. However, the precise contribution of GGCX to glucose metabolism remains to be clarified. To address this question, we generated osteoblast-specific Ggcx-deficient (i.e., conditional knockout [cKO]) mice using collagen type 1 α1 (Col1)-Cre mice. Ggcx cKO mice exhibited altered metabolism compared with their controls; serum glucose levels could be maintained with low amounts of insulin, and the weight of white adipose tissue (WAT) significantly decreased in Ggcx cKO mice. Our findings suggest that GGCX expressed in osteoblasts is critical for the maintenance of blood glucose and WAT.