Endocrine Abstracts

The relationship between bone and fat has been the subject of intense investigations over the last decade. In particular the concept that adipocytes and osteoblasts arise from the same precursor has led to significant advances in our understanding the bone marrow milieu and the in vivo responsiveness of the skeleton to nutritional, genetic and environmental stimuli. PPAR-γ lies at the center of a mesenchymal network that ultimately determines the fate of marrow stem cells and the function of adipocytes. Although PPAR-γ2 activation is essential for adipocyte differentiation, and in some cases prevents osteogenic development, this transcription factor is context specific and developmentally sensitive. Its role in brown adipogenesis and its relationship to skeletal acquisition will be reviewed. In addition, the phenotypic characterization of the skeleton in genetic ‘gain’ or ‘loss of function’ polymorphisms or mutations is remarkable and provides insights into the inter-relationship of fat to bone. Finally, we recently identified a chaperone protein that escorts PPARG into the nucleus and may link circadian rhythms to adipose and skeletal differentiation. Studies of anti-diabetic agents that enhance PPAR-γ activation but cause bone loss suggest there are multiple pathways by which this nuclear transcruiption factor can affect metabolism of bone cells. Deletion of PPARG in stromal cells using the aP2 promoter results in a provocative skeletal phenotype. Future studies are aimed at determining how hyperglycemia affects the skeleton, particularly through PPAR-γ and the role of altered circadian pathways in the syndromes of night time eating disorders, osteoporosis and obesity.