Chronological analysis of caloric restriction-induced alteration of fatty acid biosynthesis in white adipose tissue of rats.

The beneficial actions of caloric restriction (CR) could be mediated in part by metabolic remodeling of white adipose tissue (WAT). Recently, we suggested that CR for 6 months increased the expressions of proteins involved in de novo fatty acid (FA) biosynthesis in WAT of 9-month-old rats. Herein, we compared the CR-induced chronological alterations of the expression of mRNAs and/or proteins involved in FA biosynthesis in the WAT and liver of rats subjected to CR starting from 3 months of age and their age-matched controls fed ad libitum. The findings suggested that CR was more effective on FA biosynthesis in WAT than in liver. In WAT, CR markedly increased the expressions of mRNAs and/or proteins involved in FA biosynthesis, including sterol regulatory element-binding protein 1c (SREBP1c), a master transcriptional regulator of FA biosynthesis, throughout the experimental period. Interestingly, the CR-enhanced upregulation was temporally attenuated at 5 months of age. CR markedly increased the nuclear phosphorylated form of Akt only at 3.5 months of age. In contrast, CR significantly reduced the expression of leptin at 9 months of age. The CR-induced upregulation was not observed in obese fa/fa Zucker rats homozygous for nonfunctional leptin receptor. Collectively, these data indicate that the V-shaped chronological alterations in WAT are regulated via SREBP1c, which is probably activated by CR duration-dependent modulation of both insulin and leptin signaling.