PPARG and PPARA proteins, key regulators of glucose and fatty acid metabolism, are highly expressed in osteocytes. They play significant roles in the regulation of osteocyte secretome and osteocyte bioenergetics; both activities contributing to the levels of systemic energy metabolism in part through an effect on metabolic function of extramedullary and bone marrow adipocytes. The PPARs-controlled osteocyte endocrine/paracrine activities, including sclerostin expression, directly regulate adipocyte function, while the PPARs-controlled osteocyte fuel utilization and oxidative phosphorylation contribute to the skeletal demands for glucose and fatty acids, whose availability is under the control of adipocytes. Bone is an inherent element of systemic energy metabolism with PPAR nuclear receptors regulating osteocyte-adipocyte metabolic axes.