Putting the brakes on FOXO1 in fat

The Foxo1 forkhead transcription factor is a critical negative regulator of insulin action. In this issue of The EMBO Journal, Nakae and colleagues (Nakae et al, 2012) describe a novel Foxo1 Co-Repressor (FCoR) protein in adipocytes, showing that FCoR enhances the acetylation of Foxo1 to inhibit Foxo1 activity, promote adipocyte differentiation, and improve insulin sensitivity. The FoxO forkhead transcription factors have emerged as important targets of insulin and growth factor action, parti-cipating in a diverse array of biological processes. The Foxo1 isoform is a key regulator of insulin action, integrating cellular responses to changes in nutrient availability and oxidative stress (Accili and Arden, 2004). In the liver, Foxo1 induces gluconeogenesis, impairs mitochondrial metabolism, and promotes lipogenesis. In skeletal muscle, Foxo1 control