Beneficial effects of a 6-month dietary restriction are time-dependently abolished within 2 weeks or 6 months of refeeding—genome-wide transcriptome analysis in mouse liver

Abstract

Dietary restriction (DR) has been shown to exert a number of beneficial effects including the prolongation of life span. One of the mechanisms by which DR leads to these advantages seems to be the induction of endogenous antioxidant defense and stress response mechanisms. However, little is known about the persistence of DR benefits after return to an ad libitum diet. In this study, male C57BL/6 mice were fed 75% of a normal diet for 6 months (DR) followed by 6 months of ad libitum refeeding (RF) and compared to a continuously ad libitum fed control group. To study the impact of DR and RF on the liver transcriptome, a global gene expression profile was generated using microarray technology. In comparison, the DR group showed lower body weight, lower triglyceride and cholesterol levels, reduced lipid peroxidation, and a changed hepatic fatty acid pattern. mRNA transcription and activity of antioxidant and phase II enzymes, as well as metallothionein 1 gene expression, were increased and autophagy was induced. Shifting from long-term DR to RF abolished 96% of the DR-mediated changes in differential gene expression within 2 weeks, and after 6 months of refeeding all of the previously differentially expressed genes were similar in both groups. These results indicate that DR has to be maintained continuously to keep its beneficial effects.