Effects of Changes in Calorie Intake on Intestinal Nutrient Uptake and Transporter mRNA Levels in Aged Mice

Abstract

In aged, chronically calorie-restricted (CR) mice, intestinal nutrient uptake is significantly higher than in same-age ad libitum controls. Can this chronic restriction-induced enhancement of uptake be reversed by ad libitum feeding? We addressed this question by switching 32-mo-old chronically CR mice to ad libitum feeding for 4 wk (CRAL). Intestinal transport rate and total intestinal absorptive capacity for D-sugars and several nonessential L-amino acids decreased significantly in CRAL mice. In contrast, switching CR mice to an ad libitum regimen for only 3 d had no effect on intestinal nutrient transport, indicating that the negative effects of ad libitum feeding require a duration longer than the 3-d lifetime of most enterocytes. Permeability of the intestinal mucosa to L-glucose was independent of the switches in diet. Levels of the brushborder glucose transporter SGLTI, brushborder fructose transporter GLUT5, and basolateral sugar transporter GLVT2 mRNA as determined by reverse transcriptase-polymerase chain reaction in 6-, 24-, and 32-mo-old mice were each apparently independent of caloric restriction and age. We conclude that the high rates of intestinal nutrient uptake exhibited by chronically CR mice can be reversed by ad libitum feeding of only 1 mo duration. These decreases in uptake were due mainly to specific decreases in transport per unit weight of intestine and not to nonspecific decreases in intestinal mass. Changes in rates of sugar uptake induced by chronic CR and age are apparently not accompanied by changes in steady-state levels of mRNA coding for those transporters. S TUDIES on calorie restriction (CR) are highly relevant to aging because CR is the only method known to retard aging processes in mammals and to extend both mean and maximum life span in rodents (Masoro et al., 1991). Restriction of macronutrient levels (protein, fat, or carbohydrate) is a much less effective modulator of life span (Turturro et al., 1993). A 24-mo-old (median life span) mouse calorie restricted to 60% of ad libitum since 4 mo of age would have consumed over a span of 20 mo approximately 1.3 kg less food than a same age mouse fed ad libitum (AL); 1.3 kg is 65 times the body weight of a CR C57BL6 mouse. Such a large disparity in amounts of food processed affects intestinal enzyme and transporter levels (Ferraris and Diamond, 1997). Because the small intestine is the only site for nutrient digestion and absorption, studies of gut function during CR may increase our understanding of adaptive mechanisms underlying the ageretarding effects of CR.Only recently did the small intestine receive attention in studies on CR. We have previously shown that, in aged (24 mo old) mice that had been calorie restricted since 4 mo of age, intestinal transport of D-sugars and several amino acids was higher than that in same age AL controls and was comparable to that of young mice fed AL (Ferraris et al., 1993;Casirola et al., 1996). CR of several months duration is probably required before increases in intestinal nutrient transp...

Caloric restriction

“…Intestinal nutrient uptake in CR animals is significantly higher for D-sugars, L amino acids and L-glucose than in same-age AL animals (Casirola et al, 1997). Switching CR mice to AL feeding for 3 days had no effect on intestinal nutrient transport, indicating that the negative effects of AL require duration longer than the 3 days lifetime of most enterocytes.…”

“…Switching CR mice to AL feeding for 3 days had no effect on intestinal nutrient transport, indicating that the negative effects of AL require duration longer than the 3 days lifetime of most enterocytes. However, enhanced intestinal nutrient uptake under CR mice can be reversed by AL feeding for a month (Casirola et al, 1997). CR at 40% started at age 14 weeks enhances insulin stimulation of the glucose transport system independent of changes in basal glucose transport or muscle GLUT4 levels.…”

Regulation of the fructose transporter GLUT5 in health and disease

“…The small intestine regulates fructose absorption from dietary sources and, therefore, the availability of fructose to other tissues. It is also the organ system expressing the greatest amount of GLUT5 in human (13,20,47,79,81), rat (24, 35-38, 45, 72, 75, 84, 108, 112, 113, 139, 140, 147), mouse (22,33,83,107), rabbit (109), chicken (60), and horse (104). In cattle, GLUT5 expression in the intestine is significantly lower than in skeletal muscle (159), probably because this species is a foregut fermenter, and it is possible that fructose-like cellulose and other carbohydrate products are fermented in the stomach and little sugar reaches the intestinal lumen.…”

Organ-specific mediation of lifespan extension: More than a gut feeling?

“…To our knowledge, studies of genetic interventions that extend lifespan in mammalian models have not reported associated or required changes in intestinal biology. However, mice subjected to caloric restriction, a dietary intervention that robustly extends lifespan in a number of diverse invertebrates and mammals, were observed to maintain an intestinal absorption capacity for sugars and amino acids nearly twice as high as that of control mice, thereby associating enhanced and/or maintained intestinal function with lifespan extension (Casirola et al, 1997). Whether or not such an association is causal remains to be deciphered.…”