Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes

Significance Sclerostin exerts profound control over skeletal metabolism by regulating the osteoanabolic Wnt/β-catenin signaling pathway. In this study, we demonstrate that in addition to a dramatic increase in bone mass, Sost −/− mice as well as those treated with a sclerostin-neutralizing antibody exhibit a reduction in white adipose tissue mass and are protected from high fat diet feeding. This effect is associated with an increase in fatty acid oxidation and reduced de novo fatty acid synthesis in adipocytes due to increased Wnt/β-catenin signaling.