Introduction: We have shown in female rats on a severe food restricted (sFR) diet that rapid body weight (BW) loss is associated with long term cardiovascular dysfunction months after BW has returned to normal levels due to refeeding. To further investigate the long term adverse cardiovascular effects of a sFR diet, we studied a model of BW cycling in which BW is rapidly lost, gained back, then lost again, since BW cycling is common in individuals who voluntarily diet (e.g., yo-yo dieting) or those exposed involuntarily to inadequate caloric consumption (e.g., due to poverty).
Methods: Three-month-old female Fischer rats were divided into 2 groups and maintained on a control (CT; regular chow ad libitum for duration of study, n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. The sFR rats then received regular chow ad libitum for 3 weeks. This cycle of 2 weeks sFR diet plus 3 weeks of refeeding (c-sFR) was repeated twice more. Cardiac and renal function were assessed using ultrasound and insulin sensitivity was evaluated using the homeostatic model assessment of insulin resistance (HOMA-IR) index.
Results: During the 1st c-sFR, rats lost 20% of their BW after 14 days on the sFR diet; however, their BW rapidly returned to CT levels during the 3-week refeeding period. The 2nd and 3rd c-sFR led to similar BW losses (20% and 19%, respectively). No differences were observed in mean arterial pressure (MAP) and heart rate (HR) after the 3rd c-sFR compared to CT rats. However, the c-sFR rats (n=4) showed 20-40% reductions in renal artery flow (mm/s: CT, 295±12 vs c-sFR, 235±6; plt;0.05), cardiac output (mL/min: CT, 43±2 vs c-sFR, 31±3; plt;0.05) and stroke volume (mL: CT, 153±4 vs c-sFR, 89±10; plt;0.05) while the HOMA-IR index was 2.6-fold higher (AU: CT, 3±0.8 vs c-sFR, 8±1.9; plt;0.05) compared to CT rats (n=4).
Conclusion: Despite normalization of BW, MAP and HR after 3 c-sFR periods, c-sFR rats had reduced heart and kidney function and higher insulin resistance when compared to CT rats. This study suggests individuals who engage in yo-yo dieting or have experienced BW cycling due to inadequate food intake from other causes (e.g., very low food security, war, natural disasters) are at increased risk for developing cardio-metabolic disease.
IH 1R01HL119380 (KS); AHA 19POST34380744 (AS), NIH P30CA051008-22
