Chronic but not acute energy restriction increases intestinal nutrient transport in mice

Chronic energy restriction (ER) dramatically enhances intestinal absorption of nutrients by aged mice. Do adaptations in nutrient absorption develop only after extended ER or immediately after its initiation? To determine the time course of adaptations, we measured rates of intestinal glucose, fructose and proline transport 1-270 d after initiation of ER (70% of ad libitum) in 3-mo old mice. Mice of the same age that consumed food ad libitum (AL) served as controls; a third group was starved for 1 or 2 d only, to distinguish the effects of acute ER from those of starvation. Acute ER of 1, 2 and 10 d had no effect on nutrient absorption. Starvation significantly decreased intestinal mass per centimeter, thereby reducing transport per centimeter and intestinal absorptive capacity without significantly altering transport per milligram of intestine. ER for 24 d enhanced only fructose uptake, whereas ER for 270 d enhanced uptake of all nutrients by 20-100%. Despite marked differences in body weights, the wet weights of the stomach, small intestine, cecum and large intestine were generally similar in AL and ER mice, suggesting that the gastrointestinal tract was spared during ER. In contrast, the wet weights of the lungs, kidneys, spleen, heart, pancreas and liver each differed by 40-120% between ER and AL mice. Intestinal transport adaptations develop gradually during ER, and the main mechanism underlying these adaptations is a dramatic increase in transport activity per milligram tissue.