In the fed state, G0S2 is expressed at high levels in WAT when ATGL is mostly inactive and the lipolytic rate is low. In the fasted state, G0S2 is downregulated in WAT and upregulated in the liver, favoring the mobilization of FFAs through increased adipose lipolysis and their deposition as TGs in liver. G0S2 in liver acts to coordinate hepatic substrate utilization by limiting the rates of TG hydrolysis, FA oxidation, gluconeogenesis, glycogen breakdown, and ketogenesis. Upon refeeding, these fasting-induced changes in G0S2 and substrate metabolism are reversed.