The overarching hypothesis of this proposal is that obesity and positive energy balance in children promote both low bone mass accrual and risk for diabetes through events that are mechanistically associated and that involve bone as an endocrine organ. Recent studies conducted in mice have uncovered the presence of a unique "bone-fat-pancreas" axis that regulates energy homeostasis, coordinates energy partitioning between bone and adipose tissue, and impacts insulin sensitivity. The adipocyte-derived hormone leptin, elevated levels of which reflect both adiposity and positive energy balance, inhibits bone formation via sympathetic activation. Decreased bone formation in turn depresses insulin sensitivity and secretion via decreased production of undercarboxylated osteocalcin (unOC), a novel bone-derived hormone. Although data from mice are compelling, this novel pathway has not been widely tested in humans. Sparse data from adult men and women suggest that this axis is active in humans, and that unOC is regulated in part by exercise. No data are available regarding the bone-fat-pancreas axis in children. Because the foundations of body composition trajectories and metabolic "programming" are established early in the life course, childhood, particularly during early stages of growth and development, is an especially salient time period for evaluating the bone-fat-pancreas axis. With this pilot grant, we propose to gather evidence that these interrelationships exist in children. The data from this project will be used to prepare an NIH R01 proposal to conduct a lifestyle-based intervention in children aimed both at reducing risk for osteoporosis and type 2 diabetes, and at identifying the role of unOC in metabolism and tissue partitioning.