A Role for ΔFosB in Calorie Restriction-Induced Metabolic Changes

Background: Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism. Methods: After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor Delta FosB. The Delta FosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted. Results: We show that accumulation of Delta FosB in the NAc shell after CR in mice corresponds to a period of increased motivation for high fat reward and reduced energy expenditure. Furthermore, Delta FosB overexpression in this region increases instrumental responding for a high fat reward via an orexin-dependent mechanism while also decreasing energy expenditure and promoting adiposity. Conclusions: These results suggest that Delta FosB signaling in NAc mediates adaptive responses to CR.