Enhanced weight and fat loss from long-term intermittent fasting in obesity-prone, low-fitness rats.

Background: Intermittent fasting (IF) strategies have emerged as viable alternatives to traditional calorie-restricted diets. A key predictor of metabolic health and response to diet is cardiometabolic fitness, including intrinsic aerobic capacity. In a contrasting rat model of aerobic capacity-high- and low-capacity runners (HCR, LCR)-we found that the lean and physically active HCR were also more responsive to a standard calorie-restricted diet. Here, we assessed the ability of IF to induce weight loss on a background of high and low aerobic fitness accompanied by different levels of daily physical activity.

Methods: Female HCR and LCR (8 per line) were subjected to IF (alternate-day fasting) for 14 weeks. Outcomes included changes in body weight, fat and lean mass, daily physical activity, and food and water intake. After initial measurements, IF was continued, and measurements were repeated after one year of IF.

Results: All rats lost weight with IF, and LCR lost significantly more weight than HCR. This difference was primarily due to differential fat loss; loss of lean mass, on the other hand, was similar between HCR and LCR. Total food intake decreased with IF, and LCR showed lower intake than HCR only during the first 5 weeks of IF. Physical activity was suppressed by long-term IF. Physical activity increased on fed days compared to fasted days, and this pattern was more pronounced in HCR. The differential effects of IF in HCR and LCR persisted after one year of IF, with IF preventing the marked weight gain seen in ad libitum fed LCR during this time.

Conclusion: Weight and fat loss from IF was more pronounced in obesity-prone, low-aerobic capacity LCR, despite the low activity levels seen in these rats. The possibility that aerobic capacity modulates response to IF in human participants remains unexplored.