Adipose tissue is a main organ of energy metabolism, and administration of recombinant osteocalcin in mice promoted energy consumption, thus counteracting obesity and glucose intolerance.
After 6 months of Ampk inactivation, the Ampk<sup>-/-</sup> mice displayed lower serum osteocalcin levels as well as glucose intolerance and insulin resistance, as indicated by glucose tolerance and insulin tolerance tests, respectively, when compared with wild-type mice.
Animal studies have shown that an increase in the circulating concentration of osteocalcin, including via exogenous application of the protein, prevents obesity and glucose intolerance.
Together, these results underscore the involvement of bone, among other tissues, in the disruption of whole-body glucose homeostasis resulting from a HFD and the involvement of insulin and osteocalcin cross-talk in glucose intolerance.