Differential response to caloric restriction of retroperitoneal, epididymal, and subcutaneous adipose tissue depots in rats.

The beneficial actions of caloric restriction (CR) are partially mediated by metabolic remodeling of white adipose tissue (WAT). Recently, we showed that CR enhances de novo fatty acid (FA) biosynthesis and mitochondrial biogenesis, particularly in WAT. Here, to better understand the response of WAT to CR, we compare the effects of CR on three WAT depots in rats: retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous (sWAT). Computed tomography and histological analysis showed that CR reduced the volume and average size of rWAT adipocytes. In all WAT depots, CR markedly upregulated the expression of proteins involved in FA biosynthesis in fed rats. In visceral WAT (rWAT and eWAT), hormone-sensitive lipase (lipolytic form) phosphorylation was increased by CR under fed conditions, and decreased by CR under fasted conditions. Conversely, in sWAT, hormone-sensitive lipase phosphorylation was increased by CR under fasted conditions. CR enhanced the effect of feeding on AKT activity in sWAT (indicative of a positive effect on insulin sensitivity) but not in rWAT or eWAT. These data suggest that CR improves lipid metabolism in an insulin signaling-dependent manner in sWAT only. The effects of CR on adipokine (adiponectin and leptin) expression were also different among rWAT, eWAT and sWAT, and CR reduced the gene expression of M2 macrophage markers in rWAT and sWAT, but not in eWAT. We conclude that CR differentially affects the characteristics of WAT depots in rats, including adipocyte size, lipid metabolism, insulin signaling, adipocytokine profile and macrophage infiltration.

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.