Comparison of the effects of 20 days and 15 months of calorie restriction on male Fischer 344 rats.

The aim of this study was to compare, in 19-month-old male Fischer 344 rats, the influence of brief (20 days) and prolonged (approximately 15 months) calorie restriction (CR; consuming approximately 60% of ad libitum, AL, intake) on circulating levels of glucose, insulin, C-peptide, and free fatty acids (FFA); age-matched AL rats were also studied. In the prolonged CR group, there was an approximately 85% decline in fat pad masses (epididymal and retroperitoneal) compared to AL and brief CR rats (these latter groups did not differ significantly). Compared to AL levels, glucose was 15% lower with prolonged CR (p < 0.05) while the brief CR values tended to be lower (10%) than AL; the CR groups did not differ significantly. Plasma FFA levels were significantly (p < 0.05) greater (85-106%) in the brief CR group compared to each of the other groups. Plasma insulin concentrations for the CR groups were lower (p < 0.05; approximately 50-60%) than AL levels. Plasma concentrations of C-peptide (an indicator of insulin secretion) were also lower for each CR group vs AL levels, and a high correlation was found between plasma insulin and C-peptide concentrations (r2 = 0.90; p < 0.001). The C-peptide/insulin ratios for the CR groups were similar, and the value of each CR group exceeded that for the AL rats. These results demonstrate that: the CR-induced reduction in plasma insulin is attributable in large part to reduced insulin secretion; these decreases in insulin secretion and concentration are essentially undiminished when brief CR is initiated rather late in life, and the reductions are independent of substantial reductions in body fat.