In male C57BL/6 mice subjected to 40% calorie restriction, hypothalamic expression of Npy and Agrp is positively correlated with food anticipatory activity, while hypothalamic expression of Pomc and Cartpt is negatively correlated with food anticipatory activity, and these correlations are independent of total daily activity.

When food intake is reduced by 40%, fat stores shrink and hormones that signal fullness drop. This turns up genes that drive hunger and turns down genes that signal fullness in the brain's hunger center. At the same time, the brain's internal clock genes become more active and better synchronized, which sharpens the timing of food-seeking behavior. Together, these changes make the animal actively search for food at the expected mealtime, even if it isn't moving more overall.