Bone is increasingly recognized as an organ that can regulate hormones and metabolism through secreting different factors. Although bone loss and increased body fat appear to be medically linked, it is unclear if increased bone formation can alter fat metabolism. We studied this by using an engineered protein to activate signaling in the bone cells of mice. We found that total body fat was significantly reduced starting at 3 weeks of age. The mice had significantly decreased serum triacylglycerides and increased sensitivity to insulin. The mice showed resistance to fat accumulation from a high-fat diet. These findings suggest that immature bone cells can influence fat metabolism in conditions of increased bone formation and suggest a role for their use in the regulation of whole-body fat and metabolic maintenance.