SIRT1 regulates Dishevelled proteins and promotes transient and constitutive Wnt signaling.

Sirtuin 1 (SIRT1) is a class III histone deacetylase that deacetylates histone and nonhistone proteins to regulate gene transcription and protein function. Because SIRT1 regulates very diverse responses such as apoptosis, insulin sensitivity, autophagy, differentiation, and stem cell pluripotency, it has been a challenge to reconcile how it orchestrates such pleiotropic effects. Here we show that SIRT1 serves as an important regulator of Wnt signaling.

The role of sirtuin proteins in obesity.

Although the progressive metabolic changes associated with obesity are complex, it is well-recognized that obesity is a risk factor for the development of insulin resistance and type 2 diabetes. Because both obesity and type 2 diabetes are associated with insulin resistance, there is significant interest in defining the mechanistic basis for insulin resistance. Recent studies involving SIRT1, the most intensely studied sirtuin family member, have shown that it regulates many metabolic adaptations linked with obesity.