Physiological and behavioral responses to intermittent starvation in C57BL/6J mice

The dual intervention point model states that body mass is controlled by upper and lower intervention points, above and below which animals (and humans) intervene physiologically to bring their body mass back into the acceptable range. It has been further suggested that the lower intervention point may be defined by the risk of starvation, while the upper intervention point may be defined by the risk of predation. The objective of the present study was to test whether the risk of starvation determines the lower intervention point and to examine the physiological and behavioral mechanisms that underpin the regulation of body mass, when the risk of starvation is increased. Sixty-four mice were exposed to random days of complete fasting or 50% food restriction and their body mass and fat mass responses were measured. Food intake, physical activity and body temperature were measured throughout the experiment. In addition, plasma leptin and insulin, triglyceride and non-esterified fatty acids, along with hypothalamic neuropeptides gene expression in the arcuate nucleus were assessed after 13 and 42 days of treatment. We found that C57BL/6J mice increased body mass and fatness in response to a short-term (13 days) intermittent fasting, which was restored to baseline as the treatment was prolonged. In contrast, intermittently 50% food restricted mice showed no significant changes in body mass or fatness. Over the first 13 days of treatment the data were consistent with the dual intervention point model as the mice showed both increased body mass and adiposity over this period. Over the more protracted period of 42 days the effect waned and was therefore inconsistent with the model. The body mass and fat mass gains in intermittently fasted mice were mainly accounted for by increased food intake. Elevated NPY gene expression after 13 days (three 24 h fasting events) may have driven the increase in food intake. However, no changes were observed in such neuropeptides as POMC, CART, AgRP, Ob-Rb and SOCS 3 or circulating levels of leptin, insulin, NEFA and TG. Hypothermia during fasting days may have also contributed to the increase in body mass. Over 42 days of treatment (nine 24 h fasting events) cumulative food intake was not affected by intermittent starvation. However physical activity, mainly activity during the light phase was lowered suggesting an adaptation to unpredictable starvation. Overall, mice exhibited different behavioral and physiological responses to intermittent starvation depending on the duration of treatment.