Intermittent caloric restriction has the potential for improving metabolic and cardiovascular markers in rodents and humans, as well as longevity (in rodents). Furthermore, an intermittent caloric restriction regime that mimics prolonged fasting (fasting mimicking diet, FMD) has been linked to proliferation of β-cells in diabetic mice. Aim of the study was to assess the effect of FMD in female C57BL/6J mice on glucose tolerance, body and organ weight, measured at the end of the fasting and at the end of the refeeding period. We administered three weekly cycles of FMD (1st day 50%-, 2nd-3rd day 10% of daily calorie intake) followed by 4 days of refeeding ad libitum after every cycle to 20 mice at 12 weeks of age. In the second FMD cycle an intraperitoneal glucose tolerance test (IGTT) was performed either after fasting or after the 3rd refeeding day. Control animals (n=10) were fed a standard chow ad libitum. Animals were sacrificed and tissues collected after the 3rd FMD cycle, precisely 7 days after the IGTT. Compared to controls, FMD animals weighed less after the 1st, 2nd and 3rd cycle (mean differences ±SE (%): 18.9±1.8, 17.2±1.8, 15.1±1.8; p<0.001). After refeeding, bodyweight returned to levels of age matched control animals. IGTT revealed impaired glucose tolerance after fasting compared to refeeding (mean difference ±SE (mg/dL): min30: 76.4±21.8, min60: 68.7±14.3; p<0.05). Liver weight was reduced by 21.6±4.1% (p<0.001) after fasting and increased by 9.7±2.5% (p<0.001) after refeeding compared to age matched controls. Our study reveals impaired glucose tolerance at the end of the fasting period compared to the end of the refeeding period in healthy mice exposed to three cycles of FMD. Our data support previous findings that prolonged fasting rather reduces insulin secretory capacity of the ß-cell than changing insulin sensitivity, indicating to a fast adaptive cellular mechanism in ß-cells during prolonged fasting.
C. Harer: None. J. Krstic: None. P. Kotzbeck: None. C. Karacay: None. A. Prokesch: None. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K.