A new study demonstrates that the abnormal metabolism linked to obesity could be regulated in part by the interaction of two metabolic regulators, called the NAD-dependent deacetylase SIRT1 and fibroblast growth factor 21. Using experimental models, the researchers found that a lack of SIRT1 protein in the liver led to lower levels of a liver secreted protein FGF21, which resulted in an increased likelihood of developing fatty liver disease and obesity.