Role of dietary iron in maturation of rat small intestine at weaning

Abstract

The weanling process is characterized by the transition from a liquid diet poor in iron (rat milk) to a solid diet high in iron (chow pellets). To examine the effects of iron content of the weanling diet on terminal maturation of rat small intestine, suckling pups, nursed by iron-sufficient mothers, were weaned by day 16 onto a solid basal diet that was either deficient [low-iron diet (LID): 0.5 mg iron/100 g solid] or high [high-iron diet (HID) controls: 30 mg iron/100 g solid] in iron. The animals were studied during or at the end of the 4th postnatal wk. By day 17 rats weaned onto the LID exhibited an initial rise in jejunal sucrase activity as did their controls, but the activity plateau of the enzyme was reduced to a level 60% of the controls. On day 28 iron-deprived rats were anemic and showed significant decreases (P less than 0.01 compared with HID rats) in the activity of jejunal sucrase (-57%), neutral lactase (-83%), and maltase (-46%), whereas villus height, crypt depth, mucosal mass parameters, ileal acid beta-galactosidase activity, mucosal protein, and DNA synthesis rates were equivalent in LID and HID groups. The concentration of the secretory component, a glycoprotein synthesized by the intestinal crypt cell, was markedly depressed (P less than 0.01 vs. controls) in the jejunum (-54%) and ileum (-79%) of iron-deprived rats. When D-[1-14C]glucosamine was injected intraperitoneally, incorporation of the label into jejunal and ileal brush-border proteins was two to three times lower for iron-deficient rats than for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased sucrase and lactase activity in iron deficiency is accompanied by reduced gene expression and upregulation of the transcriptional repressor PDX-1

“…In agreement with previous studies, it was observed that iron-deficient Wistar rats have significantly lower sucrase and lactase activities compared with their control littermates (2,4,5,9,16,20,31,38). This decreased activity cannot be attributable to changes in kinetic properties of the enzymes as evidenced by no significant differences in K m values, inferring that it is primarily due to reduced quantities of the enzyme present in the mucosa.…”

“…One unit was defined as the ability to generate 1 mol glucose/min, and results expressed as units per gram of wet mucosa mass. Wet mucosa mass was used to calculate specific activity rather than protein content, as protein concentration in the mucosa does not significantly change during iron deficiency (4,5).…”

“…The enzymatic activity of each individual disaccharidase is influenced primarily by the dietary level of their corresponding substrate (2,12), and, under normal conditions, this level of activity is controlled by the abundance of the mRNA encoding the proteins (12,34). However, it has been shown on many occasions that dietary iron deficiency can cause a significant decrease in disaccharidase activity (2,4,5,9,16,20,31,38) and that this decrease is reversible by iron supplementation (9,20,38).…”

“…In addition, it has been shown that many other functions of the intestinal mucosa are adversely affected by iron deficiency, including a significant decrease in the secretory component (4,5), a decrease in the specific activity of diamine oxidase (4,5), and an apparent inability to manufacture membrane-bound high-molecular-weight glycoproteins (20). As such, most hypotheses explaining the mechanisms of the relationship between iron status and disaccharidase activity focus on an impaired ability to manufacture all brush border glycoproteins, either at the level of initial synthesis, posttranslational modification, or trafficking to the brush border membrane (4,5,9,20,38).…”

“…Most importantly, cell proliferation requires iron (21), yet intestinal morphology is rarely different from normal, even under severe iron deficiency (4,9,16,30). More specifically, the DNA synthesis rate of intestinal enterocytes is not affected by iron deficiency (4,27), nor is the proportion of mitotic cells in the mucosa (9).…”