Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/30/2000
Publication Date: 4/1/2001
Citation: Momcilovic, B., Reeves, P.G. 2001. Idiorrhythmic zinc dose-rate induction of intestional metallothionein in rats depends upon their nutritional status. Journal of Nutritional Biochemistry. 12:225-234. Interpretive Summary: Our body is a complex system that can adapt to a wide range of change in the amount and frequency of food intake. With a new experimental model called idiorrhythm, it is possible to study how variability in dietary food intake can affect the incorporation and fate of the essential trace element zinc in the body; a process we call metabolism. When supplied with all the necessary nutrients in their right amount and relative proportion, the body processes operate at their best and we say that the body has good nutritional status. However, the nutritional status also can be bad; it can be in deficient status, or in high status, or even toxic status, depending on the availability of nutrients in the foods we eat. In this experiment we found that a given zinc status of the body would affect its metabolic response to zinc intake. We used the laboratory rat as a model, and measured intestinal metallothionein (iMT), which responds quickly to a change in zinc status. This study showed that if the nutritional status for zinc was deficient it would take less zinc to stimulate the synthesis of iMT in the gut than when zinc status was adequate. And if zinc status was adequate, it took comparatively less zinc to induce the increase in the iMT than when zinc status was high, but not at toxic level. These findings are important because they give us useful guidelines on how to begin and to conduct clinical re-feeding programs for the malnourished and/or starving people. What we learned could base these programs on a more sound scientific principles instead of the haphazard approach used today. The experimental model we developed will be of interest for the critical evaluation of intermittent nutrient feeding or supplementation programs (like iron) in human nutrition.
Technical Abstract: The idiorrhythmic dose-rate feeding experimental model was used to study the induction of intestinal metallothionein (iMT) by zinc (Zn) in the gastrointestinal (GIT) mucosa of young growing male rats relative to their nutritional Zn status. The idiorrhythmic approach requires that the average dietary Zn concentration, the modulo (M), is kept constant across different groups over the whole experimental epoch (E). This is done by adjusting the Zn concentration of the supplemented diet to compensate for the reduction in the number of days on which this diet is fed, the latter being spread evenly over the whole experiment. Idiorrhythms (I) involve offering the diet with n times the overall Zn concentration (M) only every nth day with a Zn-deficient diet offered on other days. We studied three modulos (low-Zn, M3; adequate-Zn, M12; and high-Zn, M48), each M having 8 analogous idiorrhythms (I = Mx/1 to 8Mx/8); every I was fed over a 48-d idiorrhythmic E. Over the wide range of peak doses of dietary Zn (3 - 384 mg Zn/kg diet), the higher the modulo, the greater the capacity for iMT to be induced (M3 < M12 < M48; P<0.05). Also, the ability of Zn to induce iMT increased proportionally with the progression of the idiorrhythms from I = Mx/1 to 8Mx/8 (P<0.001). When rats were fed M3, less Zn was required to induce iMT than when they were fed M12 or M48. Thus, within the M and E limits of this study, the better the nutritional Zn status of the animal, the more Zn is required to induce iMT and vice versa. The fact that iMT was increased means that the amount of available Zn was not proportional with the actual steady state of its metabolism. This indicates that for a Zn supplementation program to be effective, it should progress from a lower to a higher Zn dose relative to the given nutritional Zn status.