Regulatory Effect of Osteocytes on Extramedullary and Bone Marrow Adipose Tissue Development and Function

Abstract

Purpose of review: This review summarizes evidence on osteocyte support of extramedullary and bone marrow adipocyte development and discusses the role of endogenous osteocyte activities of nuclear receptors peroxisome proliferator-activated receptor gamma (PPARG) and alpha (PPARA) in this support.

Recent findings: 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.

Keywords: Adipocyte; Osteocyte; PPAR alpha; PPAR gamma; Sclerostin.

Fig. 1

BMAT volume in tibia of Ctrl and γOT^KO mice. A MicroCT renderings of OsO₄ stained tibia of 7-mo-old females. B Volumetric measurements of BMAT volume in 7-mo-old female tibia. C Pearson correlation of BMAT volume (determined by microCT) and sclerostin protein levels (determined by Western blot) in osteocytes of Ctrl and γOT^KO 6.5-mo-old male mice. From Baroi et al. (ref. 4)