Loss of the Prader–Willi obesity syndrome protein necdin promotes adipogenesis

We investigated the role of necdin during adipogenic differentiation. Necdin is one of several genes inactivated in children with Prader–Willi syndrome, who are predisposed to increased adiposity at the expense of lean mass. Necdin promotes neuronal and muscle differentiation and survival through interactions with a variety of proteins, including cell surface receptors, modifiers of protein stability, and transcription factors. In pre-adipocytes, necdin over-expression inhibits adipogenesis, while reducing necdin levels enhances adipogenic differentiation in tissue culture cells. We now directly demonstrate a role for necdin in inhibiting adipogenesis using cells derived from necdin deficient mice.

► Necdin is inactivated in people with Prader–Willi obesity syndrome. ► Necdin enhances myogenic differentiation and suppresses adipogenic differentiation. ► Cells from mice lacking necdin have increased adipogenic potential. ► Necdin may inhibit adipogenesis by interacting with Wnt signaling through Dkk3.